Objective The purpose of this project is to develop a RULE-BASED APPROACH for the design and synthesis of proteomimetics of the alpha-helix and in doing so establish to what extent the structural and functional role of the alpha-helix can be reproduced with non-natural molecules in a PREDICTABLE manner We will focus on developing aromatic oligoamide proteomimetics (compounds that mimic the secondary structure from which they are derived) of one of the dominant secondary structural motifs observed in proteins the alpha-helix. Helices play a key role in mediating many protein-protein interactions, they interact with proteins and contribute residues to the resulting complex that form part of a catalytic site and they operate within the context of an entire protein structure as scaffolding upon which other helices, sheets, turns and coils pack to generate an active 3D structure. We will therefore: (i) develop a general approach for the inhibition of alpha-helix mediated protein-protein interactions, (ii) develop proteomimetics that can bind to an inactive protein and restore catalytic activity (iii) develop proteomimetics that can be covalently incorporated into the primary sequence of a protein without abolishing its function. This will lead to immense opportunities for development of new therapeutics and proteins with new functionality. More significantly, re-engineering nature to the extent of replacing whole segments of protein backbone with non-natural prostheses as proposed here will begin to answer the fundamental question: Is the astonishing structural and functional complexity achieved through precise secondary and tertiary organisation of primary protein structure confined to sequences of alpha-amino acids? Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesmedical biotechnologyimplantsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Keywords Chemical Biology Enzyme Re-engineering Foldamers Protein-Protein interactions Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-PE5 - ERC Starting Grant - Materials and Synthesis Call for proposal ERC-2009-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator UNIVERSITY OF LEEDS Address Woodhouse lane LS2 9JT Leeds United Kingdom See on map Region Yorkshire and the Humber West Yorkshire Leeds Activity type Higher or Secondary Education Establishments Administrative Contact Benjamin Williams (Mr.) Principal investigator Andrew John Wilson (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITY OF LEEDS United Kingdom EU contribution € 999 999,84 Address Woodhouse lane LS2 9JT Leeds See on map Region Yorkshire and the Humber West Yorkshire Leeds Activity type Higher or Secondary Education Establishments Administrative Contact Benjamin Williams (Mr.) Principal investigator Andrew John Wilson (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
