title: Disulfide-rich macrocyclic peptides as templates in drug design.
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.
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, QLD, Australia.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Northfield
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, QLD, Australia.
authors.forename: Conan K
authors.initials: CK
authors.lastname: Wang
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, QLD, Australia.
authors.forename: Christina I
authors.initials: CI
authors.lastname: Schroeder
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, QLD, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Durek
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, QLD, Australia.
authors.forename: Meng-Wei
authors.initials: MW
authors.lastname: Kan
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, QLD, Australia.
authors.forename: Joakim E
authors.initials: JE
authors.lastname: Swedberg
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, QLD, Australia. Electronic address: d.craik@imb.uq.edu.au.
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
mesh_terms: D004220:Disulfides / Q000737:chemistry*; D015195:Drug Design; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004220:Disulfides; D047028:Macrocyclic Compounds; D010456:Peptides, Cyclic
keywords: Cyclic peptide; Cyclotide; Disulfide bonds; Grafting