Discovery and optimization of peptide macrocycles

White, Andrew M. and Craik, David J. (2016) Discovery and optimization of peptide macrocycles. Expert Opinion on Drug Discovery, 11 12: 1151-1163. doi:10.1080/17460441.2016.1245720

Author White, Andrew M.
Craik, David J.
Title Discovery and optimization of peptide macrocycles
Journal name Expert Opinion on Drug Discovery   Check publisher's open access policy
ISSN 1746-045X
Publication date 2016-12-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1080/17460441.2016.1245720
Open Access Status Not yet assessed
Volume 11
Issue 12
Start page 1151
End page 1163
Total pages 13
Place of publication Abingdon, Oxfordshire, United Kingdom
Publisher Taylor & Francis
Language eng
Formatted abstract
Introduction: Macrocyclic peptides are generally more resistant to proteolysis and often have higher potency than linear peptides and so they are excellent leads in drug design. Their study is significant because they offer potential as a new generation of drugs that are potent and specific, and thus might have fewer side effects than traditional small molecule drugs.

Areas covered: This article covers macrocyclic drug leads based on nature-derived cyclic peptides as well as synthetic cyclic peptides and close derivatives. The natural peptides include cyclotides, sunflower-derived peptides, theta-defensins and orbitides. Technologies to make engineered cyclic peptides covered here include cyclization via amino acid linkers, CLIPS, templates, and stapled peptides.

Expert opinion: Macrocyclic peptides are promising drug leads and several are in clinical trials. The authors believe they offer key advantages over traditional small molecule drugs, as well as some advantages over protein-based ‘biologics’ such as antibodies or growth factors. These include the ability to penetrate cells and attack intracellular targets such as protein-protein interactions as well as to hit extracellular targets. Some macrocyclic peptides such as cyclotides offer the potential for production in plants, thus reducing manufacture costs and potentially increasing opportunities for their distribution to developing countries at low cost.
Keyword Cyclic peptides
Drug design
Kalata B1
Peptide macrocycles
Stapled peptides
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
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