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Chemical Structure| 166108-71-0 Chemical Structure| 166108-71-0
Chemical Structure| 166108-71-0

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CAS No.: 166108-71-0

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Fmoc-8-amino-3,6-dioxaoctanoic acid (Fmoc-NH-PEG2-CH2COOH) is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs).

Synonyms: Fmoc-NH-PEG2-CH2COOH

4.5 *For Research Use Only !

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Product Citations      Show More

Abeywardana, Maheeshi Yapa ; Whedon, Samuel D ; Lee, Kwangwoon , et al.

Abstract: Sirtuin 2 (Sirt2) is a member of the family of NAD-dependent lysine deacylases and plays important roles in regulation of the and gene expression. As a nucleocytoplasmic deacetylase, Sirt2 has been shown to target both histone and non-histone acetylated protein substrates. The central catalytic domain of Sirt2 is flanked by flexible N- and C-termini, which vary in length and composition with alternative splicing. These termini are further subject to posttranslational modifications (PTMs) including phosphorylation. Here we investigate the function of the N- and C-termini on deacetylation of nuclear substrates by Sirt2. Remarkably, we find that the C-terminus autoinhibits deacetylation, while the N-terminus enhances deacetylation of proteins and , but not nucleosomes—a chromatin model substrate. Using protein semisynthesis we characterize the effect of cell cycle-linked N-terminal phosphorylation at two major phosphorylation sites (Ser23/Ser25) and find that these further enhance protein/peptide deacetylation, with no effect on nucleosome deacetylation. Additionally, we find that VRK1, an established binding partner of both Sirt2 and nucleosomes, can stimulate deacetylation of nucleosomes by Sirt2, likely through an electrostatic mechanism. Taken together, these findings reveal multiple mechanisms regulating the activity of Sirt2, which allow for a broad range of activities across its multiple biological roles.

Purchased from AmBeed: ;

Erin M. Euliano ; Brett H. Pogostin ; Anushka Agrawal , et al.

Abstract: Toll-like receptors (TLRs) recognize pathogen- and damage-associated molecular patterns and, in turn, trigger the release of cytokines and other immunostimulatory molecules. As a result, TLR agonists are increasingly being investigated as vaccine adjuvants, though many of these agonists are small molecules that quickly diffuse away from the vaccination site, limiting their co-localization with antigens and, thus, their effect. Here, the small-molecule TLR7 agonist 1V209 is conjugated to a positively-charged multidomain peptide (MDP) hydrogel, K2, which was previously shown to act as an adjuvant promoting humoral immunity. Mixing the 1V209-conjugated K2 50:50 with the unfunctionalized K2 produces hydrogels that retain the shear-thinning and self-healing physical properties of the original MDP, while improving the solubility of 1V209 more than 200-fold compared to the unconjugated molecule. When co-delivered with ovalbumin as a model antigen, 1V209-functionalized K2 produces antigen-specific IgG titers that were statistically similar to alum, the gold standard adjuvant, and a significantly lower ratio of Th2-associated IgG1 to Th1-associated IgG2a than alum, suggesting a more balanced Th1 and Th2 response. Together, these results suggest that K2 MDP hydrogels functionalized with 1V209 are a promising adjuvant for vaccines against infectious diseases, especially those benefiting from a combined Th1 and Th2 immune response.

Keywords: vaccine adjuvant ; 1V209 ; TLR7 ; peptide hydrogel ; supramolecular

Purchased from AmBeed:

Astrid Haraldsson ;

Abstract: One of the major challenges in cancer treatment is delivering high enough doses of active substance specifically to cancer cells without accumulation in healthy organs. Pretargeting has emerged as a potential solution, where the delivery of a cancer recognizing (primary) agent and a cancer killing (secondary) agent are separated. Pretargeted cancer therapy utilizing PNA probes has proved to be a promising approach to selectively deliver toxic payloads to cancer cells while minimizing accumulation in healthy organs. The aim of this project was to develop a new set of secondary PNA probes specifically designed for PNA pretargeted delivery of cytotoxic drugs. A HER2-specific Affibody molecule, ZHER2:2891-SR-H6, was recombinantly produced in E. coli before being conjugated to a primary PNA hybridization probe, HP9, through sortase A-mediated ligation, to produce the primary agent, ZHER2:2891-SR-HP9. Circular dichroism (CD) spectroscopy confirmed the stability of the constructs with high melting temperatures of 71.2 and 73.7 °C. Surface plasmon resonance (SPR) analysis demonstrated high binding affinity to HER2, slightly affected by PNA conjugation. Three new secondary PNA hybridization probes were designed, differing mainly in prevalence and position of a hydrophilic PEG molecule. The probes were produced by solid phase peptide synthesis and conjugated to the cytotoxic drug DM1 through maleimide-cysteine coupling. Analytical RP-HPLC evaluation revealed a slightly higher apparent hydrophobicity for the probe with PEG in the main chain. All three secondary probes displayed high affinity to the primary probe with KD values between 498–505 pM. In vitro cytotoxicity studies on HER2-overexpressing cells demonstrated comparable potent cytotoxic activity for pre-incubated primary and secondary probes with IC50 values of 10–14 nM. These results indicate the successful development of three PNA-drug conjugates for pretargeted delivery of cytotoxic drugs.

Purchased from AmBeed: ; ;

Alternative Products

Product Details of [ 166108-71-0 ]

CAS No. :166108-71-0
Formula : C21H23NO6
M.W : 385.41
SMILES Code : OC(=O)COCCOCCNC(=O)OCC1C2=C(C=CC=C2)C2=C1C=CC=C2
Synonyms :
Fmoc-NH-PEG2-CH2COOH
MDL No. :MFCD01321015
InChI Key :XQPYRJIMPDBGRW-UHFFFAOYSA-N
Pubchem ID :2756092

Safety of [ 166108-71-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis [ 166108-71-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 166108-71-0 ]

[ 166108-71-0 ] Synthesis Path-Downstream   1~26

  • 1
  • (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-methylbut-5-enoic acid [ No CAS ]
  • fluorescein isothiocyanate [ No CAS ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 1311933-83-1 ]
  • [ 71989-14-5 ]
  • [ 132327-80-1 ]
  • [ 111061-56-4 ]
  • [ 166108-71-0 ]
  • C81H115N15O25S [ No CAS ]
  • 2
  • (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methylhept-6-enoic acid [ No CAS ]
  • fluorescein isothiocyanate [ No CAS ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 1311933-83-1 ]
  • [ 71989-14-5 ]
  • [ 132327-80-1 ]
  • [ 111061-56-4 ]
  • [ 166108-71-0 ]
  • C82H117N15O25S [ No CAS ]
  • 3
  • (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-methyloct-7-enoic acid [ No CAS ]
  • fluorescein isothiocyanate [ No CAS ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 1311933-83-1 ]
  • [ 71989-14-5 ]
  • [ 132327-80-1 ]
  • [ 111061-56-4 ]
  • [ 166108-71-0 ]
  • C83H119N15O25S [ No CAS ]
  • 4
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • 3-(9-carboxy-nonyloxy)benzoic acid tert-butyl ester [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{4-carboxy-4-[10-(3-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{4-carboxy-4-[10-(3-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS Method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin. Fmoc-Lys(Mtt)-OH was used in position 26, and Boc-His(trt)-OH was used in position 7. The Mtt was removedwith HFIP, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech),Fmoc-Glu-OtBu, and 3-(9-carboxy-nonyloxy)-benzoic acid tert-butyl ester were coupled using a double couplingmethod on the Liberty Peptide synthesiser.UPLC (method 04_A4_1): 10.01 minUPLC (method 08_B4_1): 8.81 minLCMS4: m/z = 978.5 (M+5H)5+, 1222.8 (M+4H)4+, 1630.1 (M+3H)3+
  • 5
  • [ 905303-12-0 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-[2-(2-{2-[10-(4-carboxyphenoxy)decanoylamino]ethoxy}ethoxy)acetyl])-EFIAWLVRGRK(Nε-[2-(2-{2-[10-(4-carboxyphenoxy)decanoylamino]ethoxy}ethoxy)acetyl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling.Preparation method: SPPS method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin.Fmoc-Lys(Mtt)-OH was used in position 26, and Boc-His(trt)-OH was used in position 7. The Mtt was removed withHFIP, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech)and 4-(9-carboxy-nonyloxy)-benzoic acid tert-butyl ester (prepared as described in Example 25, step 2 of WO2006/082204) were coupled using a double coupling method on the Liberty Peptide synthesiserUPLC (method 04_A3_1): 10.51 minLCMS4: m/z = 1085.2 (M+4H)4+, 1447.3 (M+3H)3+
  • 6
  • [ 905303-12-0 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε{2-[2-(2-{2-[2-(2-{(S)-4-Carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acet yl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin. Fmoc-Lys(Mtt)-OHwas used in position 26, and Boc-His(Trt)-OH was used in position 7. The Mtt was removed with HFIP, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech), Fmoc-Glu-OtBu,and 4-(9-carboxy-nonyloxy)-benzoic acid tert-butyl ester (prepared as described in Example 25, step 2 of WO2006/082204) were coupled using a double coupling method on the Liberty Peptide synthesiser.UPLC (method 04_A3_1): 7.19 minLCMS4: m/z = 978.5 (M+5H)5+, 1222.8 (M+4H)4+ 1630.1 (M+3H)3+
  • 7
  • [ 905303-12-0 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin. Fmoc-Lys(Mtt)-OHwas used in position 26, and Boc-His(Trt)-OH was used in position 7. The Mtt was removed with HFIP, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech), Fmoc-Glu-OtBuand 4-(9-carboxy-nonyloxy)-benzoic acid tert-butyl ester (prepared as described in Example 25, step 2 of WO2006/082204) were coupled using SPPS method D.UPLC (method 08_B4_1): Rt = 8.8 minUPLC (method 04_A3_1): Rt = 9.6 minLCMS4: 4598.0Calculated MW = 4598.2
  • 8
  • [ 905303-12-0 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-EFIAWLVRGRK(Nε-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS method BLCMS4: Rt = 2.12 min, m/z: 4916.0UPLC (method: 08_B2_1): Rt = 12.59 minUPLC (method: 04_A3_1): Rt = 10.57 min
  • 9
  • [ 905303-12-0 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-GGTFTSDVSSYLEGQAAK(Nε-[2-[2-[2-[[2-[2-[2-[[(2S)-4-carboxy-2-[10-(4-carboxyphenoxy)decanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-EFIAWLVRGRK(Nε-[2-[2-[2-[[2-[2-[2-[[(2S)-4-carboxy-2-[10-(4-carboxyphenoxy)decanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SSPS method BUPLC (method:08_B2_1): Rt = 13.193 minUPLC (method:05_B5_1): Rt = 6.685 minLCMS4: m/z: 4887; m/3:1630; m/4:1222; m/5:978
  • 10
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 27913-58-2 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[4-(4-iodophenyl)butyrylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[4-(4-iodophenyl)butyrylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual couplingPreparation method: SPPS method B, 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commerciallyavailable from Iris Biotech), <strong>[27913-58-2]4-(4-iodophenyl)butyric acid</strong> (commercially available from Aldrich) and Fmoc-Glu-OtBu were coupled using SPPS method D.UPLC (method 04_A4_1): Rt = 8.54 minUPLC (method 01_A4_2): Rt = 10.23 minLCMS4: Rt = 2.4 min, m/z = 971 (m/5) 1213 (m/44) 1617 (m/3)
  • 11
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • 3-(11-carboxy-undecyloxy)benzoic acid tert-butyl ester [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[12-(3-carboxyphenoxy)dodecanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[12-(3-carboxyphenoxy)dodecanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS Method B. The 3-(11-carboxy-undecyloxy)-benzoic acid tert-butyl ester was preparedin similar fashion as described for 3-(15-carboxy-pentadecyloxy)-benzoic acid tert-butyl ester, empoying 12-bromododecanoicacid. The final product was characterised by analytical UPLC and LC-MS with the exception that an aceticanhydride capping step was performed after the coupling of the following amino acids: Trp31, Ala25, Tyr19, Phe12 andAib8 (2? min, 65°C with 1 N Acetic acid anhydride in NMP)UPLC (method 08_B4_1): Rt = 9.449 minLCMS4: Rt = 2.37 min, m/z = m/z: 1011.88(m/4); 1264.32(m/3); 4942.24Calculated MW = 4944.608
  • 12
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 4521-22-6 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[4-(4-methylphenyl)butyrylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[4-(4-methylphenyl)butyrylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation: SPPS method B, 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commerciallyavailable from Iris Biotech), <strong>[4521-22-6]4-(4-methylphenyl)butyric acid</strong> (commercially available from ABCR) and Fmoc-Glu-OtBuwere coupled using SPPS method D.UPLC (method 01_B4_1): Rt = 9.93 minLCMS4: Rt = 2.44 min, m/z = 926(m/5) 1157(m/4) 1543(m/3)
  • 13
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 234082-00-9 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{(S)-4-carboxy-4-[2-(2-{2-[(13-carboxytridecanoylamino)]ethoxy}ethoxy)acetylamino]butyrylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{(S)-4-carboxy-4-[2-(2-{2-[(13-carboxytridecanoylamino)]ethoxy}ethoxy)acetylamino]butyrylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation: SPPS method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin. Fmoc-Lys(Mtt)-OH was usedin position 26, and Boc-His(trt)-OH was used in position 7. The Mtt was removed with HFIP manually, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech), Fmoc-Glu-OtBu andtetradecanedioc were coupled using a double coupling method on the Liberty Peptide synthesiser. The theoreticalmolecular mass was confirmed by MALDI-MS.UPLC (method 08_B4_1): Rt = 8.6 minUPLC (method 04_A3_1): Rt = 9.7 minMALDI-MS: 4788
  • 14
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 234082-00-9 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-[(S)-4-carboxy-4-{2-[2-(2-[2-(2-{2-[(13-carboxytridecanoylamino)]ethoxy}ethoxy)acetylamino]ethoxy)ethoxy] acetylamino}butyryl])-EFIAWLVRGRK(Nε-[(S)-4-carboxy-4-{2-[2-(2-[2-(2-{2-[(13-carboxytridecanoylamino)]ethoxy}ethoxy)acetylamino]ethoxy)ethoxy]acetylamino}butyryl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation: SPPS method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin. Fmoc-Lys(Mtt)-OH was used in position 26, and Boc-His(trt)-OH was used in position 7. The Mtt was removed with HFIP manually, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech), Fmoc-Glu-OtBu andtetradecanedioc were coupled using a double coupling method on the Liberty Peptide synthesiser. The theoreticalmolecular mass was confirmed by MALDI-MS.UPLC (method 08_B4_1): Rt = 8.8 minUPLC (method 04_A3_1): Rt = 10 minMALDI-MS: 4787
  • 15
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • 4-(7-carboxyheptyloxy)benzoic acid tert-butyl ester [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[8-(4-carboxyphenoxy)octanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-EFIAWLVRGRK(Nε-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[8-(4-carboxyphenoxy)octanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS method BLCMS4: Rt: 1.93 min, m/z: 4832.4; M/4: 1208.5; M/3: 1611.0UPLC (method 09_B4_1): Rt = 8.10 minUPLC (method 04_A3_1): Rt = 8.15 minUPLC (method 05_B5_1): Rt = 5.30 min
  • 16
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • 5-(12-carboxydodecyl)thiophene-2-carboxylic acid tertbutyl ester [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[13-(5-carboxythiophene-2-yl)tridecanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-EFIAWLVRGRK(Nε-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[13-(5-carboxythiophene-2-yl)tridecanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preperation method: SSPS method B. 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commerciallyavailable from Iris Biotech), Fmoc-Glu-OtBu, and 5-(12-Carboxy-dodecyl)-thiophene-2-carboxylic acid tertbutylester (prepared as described in Example 6 of WO07128815) were coupled using SSPS method D method on theLiberty synthesiser.UPLC (method 08_B4_1): Rt = 9.87 minLCMS4: m/z =1651 (m/3), 1239 (m/4), 991 (m/5)
  • 17
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • C27H44O5 [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[16-(4-carboxyphenoxy)hexadecanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[16-(4-carboxyphenoxy)hexadecanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS Method B. The final product was characterised by analytical UPLC and LC-MS withthe exception that an acetic anhydride capping step was performed after the coupling of the following amino acids:Trp31, Ala25, Tyr19, Phe12 and Aib8 (2? min, 65°C with 1 N Acetic acid anhydride in NMP). The 4-(15-carboxypentadecyloxy)benzoic acid tert-butyl ester can be prepared as decribed in Example 17 in WO07128817.UPLC (method 08_B4_1): Rt = 11.272 minUPLC (method 05_B10_1): Rt = 7.319 minLCMS4: Rt = 2.37 min, m/z = 5054.48 Calculated MW = 5056.82
  • 18
  • [ 24475-36-3 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-[4-(4-tert-butylphenyl)butyrylamino]-4-carboxybutyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-[4-(4-tert-butylphenyl)butyrylamino]-4-carboxybutyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation: SPPS method B, 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commerciallyavailable from Iris Biotech), 4-(4-t-butylphenyl)butyric acid and Fmoc-Glu-OtBu were coupled using SPPS method D.UPLC (method 08_B4_1): Rt = 9.07 minLCMS4: Rt = 2.29 min, m/z = 943 (m/5) 1179 (m/4) 1571 (m/3)
  • 19
  • [ 159610-89-6 ]
  • [ 29022-11-5 ]
  • [ 35661-39-3 ]
  • C47H62N4O4 [ No CAS ]
  • [ 71989-31-6 ]
  • [ 198561-07-8 ]
  • [ 166108-71-0 ]
  • Fmoc-Glu(Pg)-OH [ No CAS ]
  • Fmoc-Lys(Pg)-OH [ No CAS ]
  • C120H189N27O30 [ No CAS ]
  • 20
  • 2-((4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2,2,6,6-tetramethylpiperidine-1-yl)oxy)-2-methylpropanoic acid [ No CAS ]
  • [ 123639-61-2 ]
  • [ 146982-24-3 ]
  • [ 166108-71-0 ]
  • C77H104N10O22 [ No CAS ]
  • 21
  • [ 84793-07-7 ]
  • [ 188715-40-4 ]
  • [ 234081-98-2 ]
  • [ 166108-71-0 ]
  • C45H80N4O14 [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% 2-Chlorotrityl resin 100-200 mesh 1.8 mmol/g (1, 11.9 g, 21.4 mmol) was left to swell in dry dichloromethane (80 ml) for 20 minutes. A solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 5.50 g, 14.3 mmol) and N,N-diisopropylethylamine (9.44 ml, 54.2 mmol) in dry dichloromethane (70 ml) was added to resin and the mixture was shaken for 4 hours. Resin was filtered and 10 treated with a solution of N,N-diisopropylethylamine (4.97 ml, 28.5 mmol) in methanol/dichloromethane mixture (4: 1, 2 x 5 min, 2 x 57 ml). Then resin was washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,Ndimethylformamide (3 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was 15 washed with N,N-dimethylformamide (3 x 80 ml), 2-propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 11.0 g, 28.5 mmol), 0-( 6-chloro-benzotriazol-1-yi)-N,N,N', N'-tetramethyluronium tetrafluoroborate (TCTU, 10.1 g, 28.5 mmol) and N,N-diisopropylethylamine (9.93 ml, 57.0 mmol) in N,N20 dimethylformamide (80 ml) was added to resin and mixture was shaken for 2 hours. Resin was filtered and washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,N-N,N-dimethylformamide (3 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 225 propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of (S)-2-(9Hfluoren-9-ylmethoxycarbonylamino)-pentanedioic acid 1-tert-butyl ester (Fmoc-LGiu OtBu, 9.11 g, 21.4 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 7.60 g, 21.4 mmol) and N,N-diisopropylethylamine (6.71 ml, 38.5 mmol) in N,N-dimethylformamide (80 ml) was added to resin and mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (2 x 80 5 ml), dichloromethane (2 x 80 ml) and N,N-dimethylformamide (2 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 2propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of 4-[(9Hfluoren-9-ylmethoxycarbonylamino)methyl]cyclohexanecarboxylic acid (<strong>[188715-40-4]Fmoc-Trx-OH</strong>, 10 9.11 g, 21.4 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 7.60 g, 21.4 mmol) and N,N-diisopropylethylamine (6.71 ml, 38.5 mmol) in N,N-dimethylformamide (80 ml) was added to resin and mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,N-dimethylformamide (2 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 2propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of dodecanedioic acid mono-tert-butyl ester (C12(0tBu)-OH, 6.13 g, 21.4 mmol), 0-(6chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 7.61 g, 20 21.4 mmol) and N,N-diisopropylethylamine (6.71 ml, 38.5 mmol) in dichloromethane/N,N-dimethylformamide mixture (4: 1, 80 ml) was added to resin and mixture was shaken for 1.5 hour. Resin was filtered and washed with N,Ndimethylformamide (6 x 80 ml), dichloromethane (4 x 80 ml), methanol (4 x 80 ml) and dichloromethane (7 x 80 ml). The product was cleaved from resin by treatment with 25 2,2,2-trifluoroethanol (80 ml) for 18 hours. Resin was filtered off and washed with dichloromethane (4 x 80 ml), dichloromethane/2-propanol mixture (1:1, 4 x 80 ml), 2propanol (2 x 80 ml) and dichloromethane (6 x 80 ml). Solutions were combined; solvent evaporated and crude product was purified by column chromatography (Silicagel 60, 0.040-0-063 mm; eluent: dichloromethane/methanol 1:0-9:1). The pure product (2) 30 was dried in vacuo and obtained as oil. Yield: 5.40 g (42%). RF (Si02, dichloromethane/methanol 9: 1): 0.30. 1H NMR spectrum (300 MHz, CDC13, dH): 7.45-7.31 (m, 1 H); 7.10-6.97 (m, 1 H); 6.716.60 (m, 1 H); 5.70-5.58 (m, 1 H); 4.43-4.31 (m, 1 H); 4.15 (s, 2 H); 4.01 (s, 2 H); 35 3.79-3.31 (m, 16 H); 3.13-3.08 (m, 2 H); 2.28-1.79 (m, 11 H); 1.71-1.51 (m, 4 H); 1.46 (s, 9 H); 1.44 (s, 9 H); 1.25 (bs, 12 H); 1.05-0.88 (m, 2 H).LC-MS purity: 100%. LC-MS Rt (Sunfire 4.6 mm x 100 mm, acetonitrile/water 50:50 to 100:0 + 0.1% FA): 2.16 min. LC-MS m/z: 903.0 (M+H)+.
  • 22
  • [ 843666-27-3 ]
  • [ 84793-07-7 ]
  • [ 188715-40-4 ]
  • [ 166108-71-0 ]
  • C49H88N4O14 [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% 2-Chlorotrityl resin 100-200 mesh 1.8 mmol/g (1, 11.9 g, 21.4 mmol) was left to swell in dry dichloromethane (80 ml) for 20 minutes. A solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 5.50 g, 14.3 mmol) and N,N-diisopropylethylamine (9.44 ml, 54.2 mmol) in dry dichloromethane (70 ml) was added to resin and the mixture was shaken for 4 hours. Resin was filtered and 20 treated with a solution of N,N-diisopropylethylamine (4.97 ml, 28.5 mmol) in methanol/dichloromethane mixture (4: 1, 2 x 5 min, 2 x 57 ml). Then resin was washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,Ndimethylformamide (3 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 2-propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 11.0 g, 28.5 mmol), 0-( 6-chloro-benzotriazol-1-yi)-N,N,N', N'-tetramethyluronium tetrafluoroborate 5 (TCTU, 10.1 g, 28.5 mmol) and N,N-diisopropylethylamine (9.93 ml, 57.0 mmol) in N,Ndimethylformamide (80 ml) was added to resin and mixture was shaken for 2 hours. Resin was filtered and washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,N-N,N-dimethylformamide (3 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 10 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 2propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of (S)-2-(9Hfluoren-9-ylmethoxycarbonylamino)-pentanedioic acid 1-tert-butyl ester (Fmoc-LGiuOtBu, 9.11 g, 21.4 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 7.60 g, 21.4 mmol) and N,N-diisopropylethylamine (6.71 ml, 15 38.5 mmol) in N,N-dimethylformamide (80 ml) was added to resin and mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,N-dimethylformamide (2 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 220 propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of Fmoctranexamic acid (<strong>[188715-40-4]Fmoc-Trx-OH</strong>, 9.11 g, 21.4 mmol), 0-(6-chloro-benzotriazol-1-yi)N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 7.60 g, 21.4 mmol) and N,Ndiisopropylethylamine (6.71 ml, 38.5 mmol) in N,N-dimethylformamide (80 ml) was added to resin and mixture was shaken for 1 hour. Resin was filtered and washed with 25 N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,Ndimethylformamide (2 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 2-propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of hexadecanedioic acid mono-tert-butyl ester (C16(0tBu)-OH, 7.33 g, 21.4 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'tetramethyluronium tetrafluoroborate (TCTU, 7.61 g, 21.4 mmol) and N,Ndiisopropylethylamine (6.71 ml, 38.5 mmol) in dichloromethane/N,N-dimethylformamide mixture (4: 1, 80 ml) was added to resin and mixture was shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (6 x 80 ml), dichloromethane (4 x 35 80 ml), methanol (4 x 80 ml) and dichloromethane (7 x 80 ml). The product was cleaved from resin by treatment with 2,2,2-trifluoroethanol (80 ml) for 18 hours. Resin was filtered off and washed with dichloromethane (4 x 80 ml), dichloromethane/2propanol mixture (1: 1, 4 x 80 ml), 2-propanol (2 x 80 ml) and dichloromethane (6 x 80 ml). Solutions were combined; solvent evaporated and crude product was purified by column chromatography (Silicagel 60, 0.040-0-063 mm; eluent: 5 dichloromethane/methanol 1:0-9:1).Intermediate (2) was dried in vacuo and obtained as oil. Yield: 8.20 g (80%). RF (Si02, dichloromethane/methanol 9: 1): 0.20. lH NMR spectrum (300 MHz, CDC13, dH): 7.44-7.33 (m, 1 H); 7.07-6.97 (m, 1 H); 6.7210 6.63 (m, 1 H); 5.70-5.59 (m, 1 H); 4.44-4.33 (m, 1 H); 4.15 (s, 2 H); 4.01 (s, 2 H); 3.76-3.32 (m, 16 H); 3.14-3.07 (m, 2 H); 2.38-1.77 (m, 11 H); 1.71-1.50 (m, 4 H); 1.46 (s, 9 H); 1.44 (s, 9 H); 1.25 (bs, 20 H); 1.05-0.87 (m, 2 H). LC-MS purity: 100%. LC-MS Rt (Sunfire 4.6 mm x 100 mm, acetonitrile/water 50:50 to 100:0 + 0.1% FA): 15 3.56 min. LC-MS m/z: 959.0 (M+H)+.
  • 23
  • [ 843666-40-0 ]
  • C49H47N2O6Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 79-08-3 ]
  • [ 188715-40-4 ]
  • [ 166108-71-0 ]
  • 18-[[4-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-[(2-bromoacetyl)amino]-1-carboxypentyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]carbamoyl]cyclohexyl]methylamino]-18-oxooctadecanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% Synthetic protocol: Wang Fmoc-Lys(Mtt) resin 0.26 mmol/g (1, 11.7 g, 3.05 mmol) was left to swell in 5 dichloromethane (100 ml) for 45 minutes. Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 90 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). A solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 2.35 g, 6.09 10 mmol), 0-( 6-chlorobenzotriazol-1-yi)-N, N,N', N' -tetramethyluronium tetrafluoroborate (TCTU, 2.17 g, 6.09 mmol) and N,N-diisopropylethylamine (2.12 ml, 12.2 mmol) in N,Ndimethylformamide (100 ml) was added to resin and the mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90 ml) and N,N-dimethylformamide (3 x 90 ml). Fmoc group was 15 removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 90 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of {2-[2-(9Hfluoren-9-ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 2.35 g, 6.09 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium 20 tetrafluoroborate (TCTU, 2.17 g, 6.09 mmol) and N,N-diisopropylethylamine (2.12 ml, 12.2 mmol) in N,N-dimethylformamide (100 ml) was added to resin and mixture was shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90 ml) and N,N-dimethylformamide (3 x 90 ml) to obtain intermediate 1. Fmoc group was removed by treatment with 20% piperidine in N,N25 dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 90 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of (S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-pentanedioic acid 1-tert-butyl ester (Fmoc-LGiu-OtBu, 1.94 g, 4.57 mmol), 0-(6-chloro-benzotriazol-1-yi)N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 1.62 g, 4.57 mmol) and N,N30 diisopropylethylamine (1.43 ml, 8.23 mmol) in N,N-dimethylformamide (100 ml) was wo 2017/220706 PCT/EP2017/065342 72 added to resin and mixture was shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90ml) and N,Ndimethylformamide (3 x 90 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 90 ml). 5 Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of 4-[(9H-fluoren-9ylmethoxycarbonylamino )methyl]cyclohexanecarboxylic acid (<strong>[188715-40-4]Fmoc-Trx-OH</strong>, 1. 73 g, 4. 57 mmol), 0-( 6-chloro-benzotriazol-1-yi)-N,N,N', N'-tetramethyluronium tetrafluoroborate (TCTU, 1.62 g, 4.57 mmol) and N,N-diisopropylethylamine (1.43 ml, 8.23 mmol) in N,N10 dimethylformamide (100 ml) was added to resin and mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90ml) and N,N-dimethylformamide (3 x 90 ml) to obtain intermediate2. Fmoc group was removed by treatment with 20% piperidine in N,Ndimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 50 ml). Resin was washed 15 with N,N-dimethylformamide (3 x 50 ml), 2-propanol (3 x 50 ml) and dichloromethane (3 x 30 ml). Solution of octadecanedioic acid mono-tert-butyl ester (C18(0tBu)-OH, 0.85 g, 2.28 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 0.81 g, 2.28 mmol) and N,N-diisopropylethylamine (0. 72 ml, 4.11 mmol) in N,N-dimethylformamide (50 ml) was added to resin and mixture was 20 shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 50 ml), dichloromethane (3 x 50 ml) and N,N-dimethylformamide (3 x 50 ml). Mtt group was removed by treatment with 80% 1,1,1,3,3,3-hexafluoro-2-propanol in dichloromethane (2 x 10 min, 2 x 30 min, 4 x 50 ml). Resin was washed with dichloromethane (6 x 50 ml). Solution of bromoacetic acid (4.24 g, 30.5 mmol) and 25 N,N '-diisopropylcarbodiimide (DIC, 4.01 ml, 25.9 mmol) in N,N-dimethylformamide (50 ml) was added to resin and mixture was shaken for 45 minutes. Resin was filtered and washed with N,N-dimethylformamide (5 x 50 ml) and dichloromethane (10 x 50 ml). The product was cleaved from resin by treatment with trifluoroacetic acid (50 ml) for 1 hour. Resin was filtered off and washed with trifluoroacetic acid (1 x 25 ml) and 30 dichloromethane (2 x 30 ml). Solutions were combined and solvents were evaporated to dryness giving the compound as thick brownish oil. Yield: 2.18 mg (64%). 1H NMR spectrum (300 MHz, Ac0D-d4, 80C, dH): 4.72-4.55 (m, 2 H); 4.16 (s, 2 H); 4.12 (s, 2 H); 3.80-3.62 (m, 12 H); 3.58-3.44 (m, 4 H); 3.32 (t, J=6.8 Hz, 2 H); 3.15 35 (d, J=6.8 Hz, 2 H); 2.51-2.07 (m, 8 H); 2.01-1.77 (m, 6 H); ...
  • 24
  • [ 683239-16-9 ]
  • C49H47N2O6Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 79-08-3 ]
  • [ 188715-40-4 ]
  • [ 166108-71-0 ]
  • 20-[[4-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-[(2-bromoacetyl)amino]-1-carboxypentyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]carbamoyl]cyclohexyl]methylamino]-20-oxoicosanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% Synthetic protocol: Wang Fmoc-Lys(Mtt) resin 0.26 mmol/g (1, 11.2 g, 2.90 mmol) was left to swell in dichloromethane (100 ml) for 45 minutes. Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 100 15 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). A solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 2.23 g, 5.80 mmol), 0-(6-chlorobenzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 2.06 g, 5.80 mmol) and N,N-diisopropylethylamine (2.02 ml, 11.6 mmol) in N,N20 dimethylformamide (100 ml) was added to resin and the mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90 ml) and N,N-dimethylformamide (3 x 90 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 100 ml). Resin was washed with N,N-dimethylformamide (3 x 90 25 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of {2-[2-(9Hfluoren-9-ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 2.23 g, 5.80 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 2.06 g, 5.80 mmol) and N,N-diisopropylethylamine (2.02 ml, 11.6 mmol) in N,N-dimethylformamide (100 ml) was added to resin and mixture was 30 shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90ml), dichloromethane (3 x 90 ml) and N,N-dimethylformamide (3 x 90 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 100 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of (S)-2-(9H5 fluoren-9-ylmethoxycarbonylamino)-pentanedioic acid 1-tert-butyl ester (Fmoc-LGiuOtBu, 1.85 g, 4.35 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 1.55 g, 4.35 mmol) and N,N-diisopropylethylamine (1.36 ml, 7.82 mmol) in N,N-dimethylformamide (100 ml) was added to resin and mixture was shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 10 ml), dichloromethane (3 x 90ml) and N,N-dimethylformamide (3 x 90 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 100 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of <strong>[188715-40-4]4-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]cyclohexanecarboxylic acid</strong> 15 (<strong>[188715-40-4]Fmoc-Trx-OH</strong>, 1.65 g, 4.35 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'tetramethyluronium tetrafluoroborate (TCTU, 1.55 g, 4.35 mmol) and N,Ndiisopropylethylamine (1.36 ml, 7.82 mmol) in N,N-dimethylformamide (100 ml) was added to resin and mixture was shaken for 2 hours. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90ml) and N,N20 dimethylformamide (3 x 90 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 100 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of icosanedioic acid mono-tert-butyl ester (C20(0tBu)-OH, 1. 73 g, 4.35 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'25 tetramethyluronium tetrafluoroborate (TCTU, 1.55 g, 4.35 mmol) and N,Ndiisopropylethylamine (1.36 ml, 7.82 mmol) in N,N-dimethylformamide (100 ml) was added to resin and mixture was shaken for 2 hours. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90 ml), N,Ndimethylformamide (3 x 90 ml) and dichloromethane (3 x 90 ml). Mtt group was 30 removed by treatment with 80% 1,1,1,3,3,3-hexafluoro-2-propanol in dichloromethane (2 x 10 min, 2 x 30 min, 4 x 100 ml). Resin was washed with dichloromethane (6 x 90 ml) and N,N-dimethylformamide (3 x 90 ml). Solution of bromoacetic acid (8.06 g, 58.0 mmol) and N,N '-diisopropylcarbodiimide (DIC, 7.60 ml, 49.3 mmol) in N,Ndimethylformamide (100 ml) was added to resin and mixture was shaken for 40 35 minutes. Resin was filtered and washed with N,N-dimethylformamide (5 x 90 ml) and dichloromethane (12 x 90 ml). The product was cleaved from resin by treatment with trifluoroacetic acid (100 ml) for 1 hour. Resin was filtered off and washed with trifluoroacetic acid (1 x 50 ml) and dichloromethane (7 x 70 ml). Solutions were combined and solvents were evaporated to dryness giving a thick brownish oil. Yield: 3.28 g (98%). 5 1H NMR spectrum (300 MHz, Ac0D-d4, 80 C, dH): 4.68 (dd, J=8.0 and 5.4 Hz, 1 H); 4.60 (dd, J=7.9 and 5.3 Hz, 1 H); 4.16 (s, 2 H); 4.12 (s, 2 H); 3.94 (s, 2 H); 3.81-3.61 (m, 12 H); 3.59-3.44 (m, 4 H); 3.32 (t, J=6.8 Hz, 2 H); 3.14 (d, J=6.8 Hz, 2 H); 2.491.79 (m, 15 H)...
  • 25
  • [ 2424-92-2 ]
  • [ 1172127-44-4 ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2,4-dimethylpentanoic acid [ No CAS ]
  • [ 84793-07-7 ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-14-5 ]
  • [ 71989-18-9 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-35-0 ]
  • [ 47375-34-8 ]
  • [ 94744-50-0 ]
  • [ 104091-08-9 ]
  • [ 76-05-1 ]
  • (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
  • [ 166108-71-0 ]
  • Fmoc-Glu(pg)-OH [ No CAS ]
  • Y-Aib-EGT-αMeF(2F)-TSDYSI-αMeL-LDEK((2-[2-(2-aminoethoxy)ethoxy]acetyl)2-(γGlu)-CO-(CH2)18-CO2H)AQ-Aib-EFI-(D-Glu)-YLIEGGPSSGAPPPS-NH2 trifluoroacetic acid salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: The peptide backbone of Peptide 1 is synthesized usingFluorenylrnethyloxycarbonyi (Fmoe)/tert-Butyl (t-Bu) chemistry on a Symphony X peptide synthesizer (Gyros Protein Technologies. Tucson, AZ).The resin consists of 1% DVB cross-linked polystyrene (Fmoc-Rink-MBHA Low Loading resin, 100-200 mesh, EMD Millipore) at a substitution of 0.3-0.4 meq/g.Standard side-chain protecting groups were used. Fmoc-Lys(Mtt)-OH is used for the lysine at position 17 and Boc-Tyr(tBu)-QH) was used for the tyrosine at position 1. Frnoc groups are removed prior to each coupling step (2 x 7 minutes) using 20% piperidine in DMF. All standard amino acid couplings are performed for 1 hour to a primary amine and 3 hour to a secondary amine, using an equal molar ratio of Fmoc amino acid (0.3 mM), diisopropyicarbodiimide (0.9 mM) and Qxyma (0.9 mM), at a 9-fold molar excess over the theoretical peptide loading. Exceptions are couplings to C -methylated amino acids, which are coupled for 3 hours. After completion of the synthesis of the peptide backbone, the resin is thoroughly washed with DCM for 6 times to remove residual DMF. The Mtt protecting group on the lysine at position 17 is selectively removed from the peptide resin using two treatments of 30% hexafuoroisopropanol (Oakwood Chemicals) in DCM (2 x 40-minute treatment).Subsequent attachment of the fatty acid-linker moiety is accomplished by coupling of 2-[2-(2-Fmoc-amino-ethoxy)-ethoxy]-acetic acid (Fmoc-AEEA-OH, ChemPep, hie.), Fmoe-glutamie acid or-t-butyl ester (Fmoc-Glu-OtBu, Ark Pharm, Inc.), eicosanedioic acid (WuXi AppTec, Shanghai, China). 3-Fold excess of reagents (AA: PyAQP: DIPEAM : 1 : 1 mol/mol) are used for each coupling that is I -hour long.After the synthesis is complete, the peptide resin is washed with DCM, and then thoroughly air-dried. The dry' resin is treated with 10 mL of cleavage cocktail(trifuoroaeetie acid: water: triisopropylsilane, 95:2,5:2.5 v/v) for 2 hours at room temperature. The resin is filtered off, washed twice each with 2 mL of neat T'FA, and the combined filtrates are treated with 5-fold excess volume of cold diethyl ether (-20C) to precipitate the crude peptide. The peptide/ether suspension is then centrifuged at 3500 rpm for 2 min to form a solid pellet, the supernatant is decanted, and the solid pellet is triturated with ether two additional times and dried in vacuo. The crude peptide is solubilized in 20% aeetonitrile/20%Acetic acid/60%water and purified by RP- HPLC on a Luna 5 /.mi Phenyl-Hexyl preparative column (21 x 250 mm, Phenomenex) with linear gradients of 100% acetonitrile and 0.1% TF A/ water buffer system (30-50% acetonitrile in 60 min). The purity of peptide is assessed using analytical RP-HPLC and pooling criteria is >95%. The main pool purity of compound 1 is found to be 98.0%. Subsequent lyophilization of the final main product pool yielded the lyophilized peptide TFA salt.The molecular weight is determined by LC- MS (obsd: M+3 =1657.2; Calc M+3=1657.0).
  • 26
  • [ 683239-16-9 ]
  • [ 1172127-44-4 ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2,4-dimethylpentanoic acid [ No CAS ]
  • [ 84793-07-7 ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-14-5 ]
  • [ 71989-18-9 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-35-0 ]
  • [ 47375-34-8 ]
  • [ 71989-20-3 ]
  • [ 94744-50-0 ]
  • [ 104091-08-9 ]
  • [ 76-05-1 ]
  • (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
  • [ 166108-71-0 ]
  • Y-Aib-EGT-αMeF(2F)-TSDYSI-αMeL-LDEK((2-[2-(2-aminoethoxy)ethoxy]acetyl)<SUB>2</SUB>-(γ-Glu)-CO-(CH2)<SUB>18</SUB>-CO<SUB>2</SUB>H)AQ-Aib-EFI-(D-Glu)-YLIEGGPSSGAPPPS-NH<SUB>2</SUB><SUB> trifluoroacetic acid salt</SUB> [ No CAS ]
YieldReaction ConditionsOperation in experiment
The peptide backbone of Example 1 is synthesized using Fluorenylmethyloxycarbonyl (Fmoc)/tert-Butyl (t-Bu) chemistry on a Symphony X peptide synthesizer (Gyros Protein Technologies. Tucson, Ariz.). The resin consists of 1% DVB cross-linked polystyrene (Fmoc-Rink-MBHA Low Loading resin, 100-200 mesh, EMD Millipore) at a substitution of 0.3-0.4 meq/g. Standard side-chain protecting groups were used. Fmoc-Lys(Mtt)-OH is used for the lysine at position 17 and Boc-Tyr(tBu)-OH) was used for the tyrosine at position 1. Fmoc groups are removed prior to each coupling step (2×7 minutes) using 20% piperidine in DMF. All standard amino acid couplings are performed for 1 hour to a primary amine and 3 hour to a secondary amine, using an equal molar ratio of Fmoc amino acid (0.3 mM), diisopropylcarbodiimide (0.9 mM) and Oxyma (0.9 mM), at a 9-fold molar excess over the theoretical peptide loading. Exceptions are couplings to Calpha-methylated amino acids, which are coupled for 3 hours. After completion of the synthesis of the peptide backbone, the resin is thoroughly washed with DCM for 6 times to remove residual DMF. The Mtt protecting group on the lysine at position 17 is selectively removed from the peptide resin using two treatments of 300 hexafluoroisopropanol (Oakwood Chemicals) in DCM (2×40-minute treatment). Subsequent attachment of the fatty acid-linker moiety is accomplished by coupling of 2-[2-(2-Fmoc-amino-ethoxy)-ethoxy]-acetic acid (Fmoc-AEEA-OH, ChemPep, Inc.), Fmoc-glutamic acid alpha-t-butyl ester (Fmoc-Glu-OtBu, Ark Pharm, Inc.), mono-OtBu-eicosanedioic acid (WuXi AppTec, Shanghai, China). 3-Fold excess of reagents (AA:PyAOP:DIPEA=1:1:1 mol/mol) are used for each coupling that is 1-hour long. After the synthesis is complete, the peptide resin is washed with DCM, and then thoroughly air-dried. The dry resin is treated with 10 mL of cleavage cocktail (trifluoroacetic acid:water:triisopropylsilane, 95:2.5:2.5 v/v) for 2 hours at room temperature. The resin is filtered off, washed twice each with 2 mL of neat TFA, and the combined filtrates are treated with 5-fold excess volume of cold diethyl ether (-20 C.) to precipitate the crude peptide. The peptide/ether suspension is then centrifuged at 3500 rpm for 2 min to form a solid pellet, the supernatant is decanted, and the solid pellet is triturated with ether two additional times and dried in vacuo. The crude peptide is solubilized in 20% acetonitrile/20% Acetic acid/60% water and purified by RP-HPLC on a Luna 5 mum Phenyl-Hexyl preparative column (21*250 mm, Phenomenex) with linear gradients of 100% acetonitrile and 0.1% TFA/water buffer system (30-50% acetonitrile in 60 min). The purity of peptide is assessed using analytical RP-HPLC and pooling criteria is >95%. The main pool purity of compound 1 is found to be 98.0%. Subsequent lyophilization of the final main product pool yielded the lyophilized peptide TFA salt. The molecular weight is determined by LC-MS (obsd. M+3=1657.2; Calc M+3=1657.0).
 

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