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Macrocyclic peptide-based compounds (mol wt. ~1000-3000) are a highly underexploited class of molecules in drug development. In particular, stapled peptides are promising inhibitors of protein-protein interactions that are the drivers of many cancers. The stapling process involves the cyclisation of two unnatural amino acid side chains, imparting conformational rigidity which can improve proteolytic stability and cellular uptake. Our chemical approach to stapling involves using a double-click reaction, using a dialkynyl linker to bridge two azido amino acids. In this project, we will establish a new strategy for synthesising vast libraries of macrocyclic ‘stapled’ peptides, using a combination of bioorthogonal chemistry and recombinant technologies (see Nat. Protoc. 2015, 10, 585-594; Angew. Chem. Int. Ed. 2015, 54, 15410-15413). The resulting compound library will then be screened in cellular and in vitro assays to identify new anti-cancer drug candidates.
These projects are suited for students who are interested in the interface between chemistry and biology. Previous experience in organic chemistry or molecular biology is desirable. Feel free to contact Dr Lau to learn more about the project, the application process, and potential funding opportunities.
In addition to the academic requirements set out in the Science Postgraduate Handbook, you may be required to satisfy a number of inherent requirements to complete this degree. Example of inherent requirement may include:
The opportunity ID for this research opportunity is 2401