Synthesis and protein engineering applications of cyclotides

Qu, Haiou, Smithies, Bronwyn J. , Durek, Thomas and Craik, David J. (2017) Synthesis and protein engineering applications of cyclotides. Australian Journal of Chemistry, 70 2: 152-161. doi:10.1071/CH16589


Author Qu, Haiou
Smithies, Bronwyn J.
Durek, Thomas
Craik, David J.
Title Synthesis and protein engineering applications of cyclotides
Journal name Australian Journal of Chemistry   Check publisher's open access policy
ISSN 1445-0038
0004-9425
Publication date 2017-02-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1071/CH16589
Open Access Status Not yet assessed
Volume 70
Issue 2
Start page 152
End page 161
Total pages 10
Place of publication Clayton, VIC, Australia
Publisher C S I R O Publishing
Language eng
Abstract Cyclotides are a group of plant-derived peptides with a head-to-tail cyclized backbone that is stabilized by three knotted disulfide bonds. Their exceptional stability and tolerance for residue substitutions have led to interest in their application as drug design scaffolds. To date, chemical synthesis has been the dominant methodology for producing cyclotides and their analogues. Native chemical ligation is the most common strategy to generate the cyclic backbone and has been highly successful at producing a wide range of cyclotides for studies of structure-activity relationships. Both this and other chemical approaches require a specific linker at the C-terminus and typically involve a non-directed folding (disulfide oxidation) regimen, which can sometimes be a limiting factor in final yields. Following the recent discovery of enzymes involved in peptide cyclization in planta, site-specific and highly efficient enzymatic ligations have been used for synthetic cyclotide backbone cyclization. In this review, chemical synthesis strategies and approaches involving cyclization via enzymes for the production of cyclotides are described.
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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