Gap 26
Gap26 (Val-Cys-Tyr-Asp-Lys-Ser-Phe-Pro-Ile-Ser-His-Val-Arg) is a connexin mimetic peptide, corresponding to residues 63-75 of connexin 43, which is a gap junction blocker.
Connexins, or gap junctions, are a family of structurally-related transmembrane proteins. Gap junctions contain channels that allow the passage of ions and small molecules between adjacent cells molecules. Calcium and inositol phosphates are among the second messengers that can pass through gap junction channels. [1] It was showed that gap26 attenuates rhythmic contractile activity of rabbit arterial smooth muscle (IC50 = 28.4 mM). It also blocks movement of IP3-induced ATP and Ca2+ across connexin hemichannels, i.e. hexameric channels yet to dock with partners in aligned cells and to generate the gap junction cell–cell conduit. [2]
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Fig. 1: Formula of Gap26
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Fig. 2:?Function of Gap26.
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Ref:
1. Boitano, S. and H. Evans Am. J. Physiol. Lung Cell Mol. Physiol. 279, L623 (2000).
2. T. Desplantez, V. Verma, L. Leybaert, W.H. Evans, R. Weingart, Gap26, a connexin mimetic peptide, inhibits currents carried by connexin43 hemichannels and gap junction channels, Pharmacological Research, Volume 65, Issue 5, May 2012, Pages 546-552.
- 1. Weiqi Zeng, Zhizhao Deng, et al. "Downregulation of connexin 43-based gap junctions underlies propofol-induced excessive relaxation in hypertensive vascular smooth muscle cells." Cell Commun Signal. 2023 Jun 28;21(1):163. PMID: 37381027
- 2. Chenyu Liang, Qian Zhang, et al. "Human cancer cells generate spontaneous calcium transients and intercellular waves that modulate tumor growth." Biomaterials. 2022 Oct 5;290:121823. PMID: 36209577
- 3. Xuqing Qin, Wenjun He, et al. "Inhibition of Connexin 43 reverses ox-LDL-mediated inhibition of autophagy in VSMC by inhibiting the PI3K/Akt/mTOR signaling pathway." PeerJ. 2022 Mar 16;10:e12969. PMID: 35313522
- 4. Xiao-Dong Tao, Zhao-Rui Liu, et al. "Connexin43 hemichannels contribute to working memory and excitatory synaptic transmission of pyramidal neurons in the prefrontal cortex of rats." Life Sci. 2021 Dec 1;286:120049. PMID: 34662549
- 5. Guo-Li Zhao, Hong Zhou, et al. "Modulation of Rac1/PAK1/connexin43-Mediated ATP Release from Astrocytes Contributes to Retinal Ganglion Cell Survival in Experimental Glaucoma." Research Square. rs-770147/v1.
- 6. Rui-Juan Gao, Ai-Mei Zhang, et al. "The promoting role of Cx43 on the proliferation and migration of arterial smooth muscle cells for angiotensin II-dependent hypertension." Pulm Pharmacol Ther. 2021 Oct;70:102072. PMID: 34428599
- 7. Cai Qing, Zhao Xinyi, et al. "The Specific Connexin 43–Inhibiting Peptide Gap26 Improved Alveolar Development of Neonatal Rats With Hyperoxia Exposure." Front Pharmacol. 2021 Jul 5;12:587267. PMID: 34290603
- 8. Zhou Z, Ni J, et al. "Angiotensin II induces RAW264. 7 macrophage polarization to the M1-type through the connexin 43/NF-κB pathway." Mol Med Rep. 2020;21(5):2103-2112. PMID: 32186758
- 9. Steven Condamine. "Organisation anatomique et r?le du couplage astrocytaire dans l’activité rythmique du noyau sensoriel du trijumeau." Université de Montréal. 2019.
- 10. Wang M, Wu Y, et al. "Rutaecarpine prevented ox-LDL-induced VSMCs dysfunction through inhibiting overexpression of connexin 43." Eur J Pharmacol. 2019 Jun 15;853:84-92. PMID: 30880182
- 11. Mederos S, Hernández-Vivanco A, et al. "Melanopsin for precise optogenetic activation of astrocyte-neuron networks." Glia. 2019 Jan 11. PMID: 30632636
- 12. Zhang X, Chen D, et al. "Involvement of sphingosine-1-phosphate receptors 2/3 in IR-induced sudden cardiac death." Heart Vessels. 2019 Jan 2. PMID: 30604190
- 13. Condamine S, Lavoie R, et al. "Functional Rhythmogenic Domains Defined by Astrocytic Networks in the Trigeminal Main Sensory Nucleus." Glia. 2017 Oct 23. PMID: 29058348
- 14. Yang G, Peng X, et al. "Involvement of connexin 43 phosphorylation and gap junctional communication between smooth muscle cells in vasopressin-induced ROCK-dependent vasoconstriction after hemorrhagic shock." Am J Physiol Cell Physiol. 2017 Oct 1;313(4):C362-C370. PMID: 28974518
- 15. Li X, Jiang S, et al. "Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model." Front Cell Neurosci. 2017 Jul 17;11:207. PMID: 28769766
- 16. Chu H, Huang C, et al. "Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and Astragaloside IV via Down-Regulating Connexin 43." Phytother Res. 2017 Jul 28. PMID: 28752625
- 17. Zhou, Ziyi, et al. "Protection of erythropoietin against ischemic neurovascular unit injuries through the effects of connexin43." Biochemical and biophysical research communications 458.3 (2015): 656-662. PMID: 25684187
| Physical Appearance | A solid |
| Storage | Desiccate at -20°C |
| M.Wt | 1550.79 |
| Cas No. | 197250-15-0 |
| Formula | C70H107N19O19S |
| Synonyms | Val-Cys-Tyr-Asp-Lys-Ser-Phe-Pro-Ile-Ser-His-Val-Arg |
| Solubility | insoluble in EtOH; ≥155.1 mg/mL in H2O with ultrasonic; ≥77.55 mg/mL in DMSO with gentle warming and ultrasonic |
| SDF | Download SDF |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
ECV304 cells |
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Preparation method |
The solubility of this peptide in sterile water is >10 mM. Stock solution should be splited and stored at -80°C for several months. |
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Reaction Conditions |
0.25mg/ml, 30min |
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Applications |
Preventing the InsP3-triggered calcium increase by ester loading the cells with the calcium chelator BAPTA reduced the InsP3-triggered ATP release back to the control level. Incubation of the cells with gap 26 completely abolished the InsP3-triggered ATP response and reduced the ATP release to below the control level, indicating that the basal ATP release is also affected. |
| Animal experiment: [2] | |
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Animal models |
Female Sprague-Dawley rats |
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Dosage form |
300 μM, 45 min |
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Applications |
The rats were prepared with closed cranial windows 24 h before the study. A 10-mm-diameter craniotomy was performed over the skull midline. The dura was removed carefully to keep the sagittal sinus intact. An 11-mm-diameter glass window outfitted with three ports was glued to the skull using cyanoacrylate. The skin overlying the window was sutured, and the animals were permitted to recover. On the day of study, three stainless steel screws were inserted into the skull, along the periphery of the cranial window, for electroencephalogram (EEG) recording. Cannulae were then connected to the three ports. The rats were subjected to one of two neuronal activation paradigms: SNS or bicuculline-induced seizure. Following the initial measurement of pial arteriolar diameter changes during SNS or during bicuculline exposure, baseline conditions were reestablished. After 20 min, a suffusion of gap-26 was initiated. Forty-five minutes later, the neural activation was repeated. Exposure to the Cx40/Cx37 inhibitory peptide, gap-26 (300 μM), was without effect on bicuculline- or SNS-induced pial arteriolar dilations. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Braet K, Vandamme W, Martin P E M, et al. Photoliberating inositol-1, 4, 5-trisphosphate triggers ATP release that is blocked by the connexin mimetic peptide gap 26. Cell calcium, 2003, 33(1): 37-48. [2] Xu H L, Mao L, Ye S, et al. Astrocytes are a key conduit for upstream signaling of vasodilation during cerebral cortical neuronal activation in vivo. American Journal of Physiology-Heart and Circulatory Physiology, 2008, 294(2): H622-H632. |
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| Description | Gap26 (Val-Cys-Tyr-Asp-Lys-Ser-Phe-Pro-Ile-Ser-His-Val-Arg) is a connexin mimetic peptide, corresponding to residues 63-75 of connexin 43, which is a gap junction blocker. | |||||
| Targets | ||||||
| IC50 | ||||||
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