Disulfide-rich macrocyclic peptides as templates in drug design

Susan E Northfield; Conan K Wang; Christina I Schroeder; Thomas Durek; Meng-Wei Kan; Joakim E Swedberg; David J Craik

doi:10.1016/j.ejmech.2014.03.011

Disulfide-rich macrocyclic peptides as templates in drug design

Eur J Med Chem. 2014 Apr 22:77:248-57. doi: 10.1016/j.ejmech.2014.03.011. Epub 2014 Mar 6.

Authors

Susan E Northfield¹, Conan K Wang¹, Christina I Schroeder¹, Thomas Durek¹, Meng-Wei Kan¹, Joakim E Swedberg¹, David J Craik²

Affiliations

¹ The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, QLD, Australia.
² The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, QLD, Australia. Electronic address: d.craik@imb.uq.edu.au.

PMID: 24650712
DOI: 10.1016/j.ejmech.2014.03.011

Abstract

Recently disulfide-rich head-to-tail cyclic peptides have attracted the interest of medicinal chemists owing to their exceptional thermal, chemical and enzymatic stability brought about by their constrained structures. Here we review current trends in the field of peptide-based pharmaceuticals and describe naturally occurring cyclic disulfide-rich peptide scaffolds, discussing their pharmaceutically attractive properties and benefits. We describe how we can utilise these stable frameworks to graft and/or engineer pharmaceutically interesting epitopes to increase their selectivity and bioactivity, opening up new possibilities for addressing 'difficult' pharmaceutical targets.

Keywords: Cyclic peptide; Cyclotide; Disulfide bonds; Grafting.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Disulfides / chemistry*
Drug Design*
Macrocyclic Compounds / chemical synthesis
Macrocyclic Compounds / chemistry
Macrocyclic Compounds / pharmacology*
Molecular Conformation
Peptides, Cyclic / chemical synthesis
Peptides, Cyclic / chemistry
Peptides, Cyclic / pharmacology*

Substances

Disulfides
Macrocyclic Compounds
Peptides, Cyclic