Issue 6, 2021

Cyclisation strategies for stabilising peptides with irregular conformations

Abstract

Cyclisation is a common synthetic strategy for enhancing the therapeutic potential of peptide-based molecules. While there are extensive studies on peptide cyclisation for reinforcing regular secondary structures such as α-helices and β-sheets, there are remarkably few reports of cyclising peptides which adopt irregular conformations in their bioactive target-bound state. In this review, we highlight examples where cyclisation techniques have been successful in stabilising irregular conformations, then discuss how the design of cyclic constraints for irregularly structured peptides can be informed by existing β-strand stabilisation approaches, new computational design techniques, and structural principles extracted from cyclic peptide library screening hits. Through this analysis, we demonstrate how existing peptide cyclisation techniques can be adapted to address the synthetic design challenge of stabilising irregularly structured binding motifs.

Graphical abstract: Cyclisation strategies for stabilising peptides with irregular conformations

Article information

Article type
Review Article
Submitted
18 mar 2021
Accepted
12 apr 2021
First published
28 apr 2021

RSC Med. Chem., 2021,12, 887-901

Cyclisation strategies for stabilising peptides with irregular conformations

Q. N. Vu, R. Young, H. K. Sudhakar, T. Gao, T. Huang, Y. S. Tan and Y. H. Lau, RSC Med. Chem., 2021, 12, 887 DOI: 10.1039/D1MD00098E

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