New Approaches to Peptide Stapling

Peptide staples are an emerging class of 'chemologic' molecule which represent hybrids of chemical and biological constructs, and have wide ranging applications from target validation to new therapeutics.

Currently, only a limited palette of synthetic approaches are employed to create the 'staple' and hence modulate secondary structure.

The proposed study aims to exploit novel reactivity identified in our laboratories using the a reactive intermediate generated photochemically in order to create a modular, heterocyclic-based staple with tuneable molecular and functional properties.

The approach will be exemplified using a workhorse biological system of disease relevance, enabling comparison with current stapling approaches. The basic chemistry developed is also suitable to forge new carbon-carbon bonds in molecules of biological interest.

This aspect of the proposal will also be explored to identify conditions that may be used to create C-C bonds using mild, light mediated conditions before applying the same chemistry to the synthesis of the macromolecular constructs described above.