Rotaxanes with a photoresponsive macrocycle modulate the lipid bilayers of large and giant unilamellar vesicles
Conthagamage, Udyogi NK
;
Rajeshwar T, Rajitha
;
van der Ham, Stijn
, et al.
Commun. Chem.,2024,7,255.
DOI:
10.1038/s42004-024-01343-8
PubMed ID:
39516242
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Abstract: Rotaxanes equipped with actuators hold great potential for developing highly functional molecular machines. Such systems could significantly enhance our ability to study and manipulate biological and artificial membranes. Here, we introduce a rotaxane with a ring featuring two azobenzene photoswitches, which retain their photoreversibility and can be stochastically shuttled along the axle in solution. Studies in model bilayers, supported by molecular dynamics simulations, show how azobenzene photoswitching alters the interaction of rotaxanes with surrounding lipids, leading to changes in lipid packing. Such changes in the lipid bilayer were leveraged to induce the light-triggered release of sulforhodamine B from large unilamellar vesicles. Additionally, light activation of the rotaxanes is shown to induce reversible contraction and expansion of giant unilamellar vesicles. The results provide novel insights into the interactions and operation of rotaxanes in lipid bilayers and their impact on membrane properties. This will aid in developing systems for precise membrane manipulation for applications in biomedicine and bioengineering.
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4235-95-4
Probing Amyloid-beta Aggregation Using Paramagnetic Complexes
Julius Adamson
;
The University of Sydney,2024.
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Abstract: Alzheimer’s disease is the leading cause of dementia and is creating a growing economic and social burden on the aging global population. The drugs approved for the treatment of Alzheimer’s disease are only able to slow the onset of the disease. Attempts to develop treatments which halt, or reverse, cognitive decline have proven unsuccessful.
Amyloid-β is a neuronally-derived peptide which has been implicated in Alzheimer’s disease for over three decades. Amyloid-β aggregates to form fibrils which eventually deposit as amyloid plaques in the brain and has remained a popular target for the treatment of Alzheimer’s disease. Treatments that inhibit the production of amyloid-β, or remove the end-stage aggregates have not been able to ameliorate the symptoms of the disease. The demonstrated toxicity of intermediate oligomers of amyloid-β has caused research to shift towards understanding and disrupting the aggregation process
itself.
This thesis focuses on the synthesis of bis-perphenazine cyclam conjugates and their complexes, which were identified in a screen of compounds that inhibit the aggregation of amyloid-β. Chapter 2 describes the development of a scalable synthesis of these compounds and further characterises their biological activity. It was found that these compounds inhibited aggregation by interacting with monomeric Aβ and that they could reduce the toxicity of Aβ towards cultured neuronal cells.
Chapters 3 and 4 describe the development of a series of probe compounds which can act as paramagnetic NMR probes to investigate how the compounds bind to amyloid-β.Attempts at synthesising bis-perphenazine lanthanide probes are described in Chapter
3. Chapter 4 describes the synthesis of a series of lanthanide probes containing one perphenazine pendant. The compounds were shown to disrupt the aggregation of Aβ in vitro but attempts to identify how the probes interacted with monomeric Aβ using paramagnetic relaxation enhancement were unsuccessful.
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52093-30-8 ;
510758-28-8 ;
52093-25-1
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