A modular synthesis of conformationally preorganised extended β-strand peptidomimetics

Journal article

A promising strategy for mediating protein-protein interactions is the use of non-peptidic mimics of secondary structural protein elements, such as the α-helix. Recent work has expanded the scope of this approach by providing proof-of-principle scaffolds that are conformationally biased to mimic the projection of side-chains from one face of another common secondary structural element-the β-strand. Herein, we present a synthetic route that has key advantages over previous work: monomers bearing an amino acid side-chain were pre-formed before rapid assembly to peptidomimetics through a modular, iterative strategy. The resultant oligomers of alternating pyridyl and six-membered cyclic ureas accurately reproduce a recognition domain of several amino acid residues of a β-strand, demonstrated herein by mimicry of the i, i+2, i+4 and i+6 residues.

Authors: Yamashita, T; Knipe, P; Busschaert, N; Thompson, S; Hamilton, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Chemistry - A European Journal
• Volume: 21
• Issue: 42
• Pages: 14699-14702
• Publication date: 2015-08-17
• Acceptance date: 2015-08-17
• DOI: 10.1002/chem.201501366
• EISSN: 1521-3765
• ISSN: 0947-6539
• Language: English
• Keywords: extended conformations; foldamers; dipolar repulsion; protein-protein interactions; inhibitors