Native chemical ligation applied to the synthesis and bioengineering of circular peptides and proteins

Clark, Richard J. and Craik, David J. (2010) Native chemical ligation applied to the synthesis and bioengineering of circular peptides and proteins. Biopolymers, 94 4: 414-422. doi:10.1002/bip.21372

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Author Clark, Richard J.
Craik, David J.
Title Native chemical ligation applied to the synthesis and bioengineering of circular peptides and proteins
Journal name Biopolymers   Check publisher's open access policy
ISSN 0006-3525
Publication date 2010
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1002/bip.21372
Volume 94
Issue 4
Start page 414
End page 422
Total pages 9
Editor Gary D. Glick
Place of publication Hoboken, NJ, U.S.A.
Publisher Wiley Interscience
Collection year 2011
Language eng
Formatted abstract
Native chemical ligation methodology developed in the laboratory of Stephen Kent is a versatile approach to the linkage of peptide fragments using a native peptide bond. It is readily adaptable to the task of joining the N- and C-termini of peptides to produce cyclic molecules and we have used it for the cyclization of a range of disulfide-rich peptides. Specifically, it has been valuable for the synthesis of cyclotides, naturally occurring peptides characterized by a head-to-tail cyclized backbone and a knotted arrangement of three conserved disulfide bonds. Cyclotides have a diverse range of biological activities, including anti-HIV, antimicrobial, and insecticidal activities. They are ultrastable owing to their cyclic cystine knot motif, and native chemical ligation methodology has been invaluable in the synthesis of a range of native and modified cyclotides to explore their structure-activity relationships and applications in drug design. Similar studies have also been applied to a smaller cyclic peptide produced in sunflower seeds, sunflower trypsin inhibitor-1, which also shows promise as a template in drug design applications. We have also found native chemical ligation to be a valuable methodology for the cyclization of conotoxins, small disulfide-rich peptides from the venoms of marine cone snails. Conotoxins target a range of ions channels and receptors and are exciting leads in drug design applications. The synthetic cyclization of conotoxins with peptide linkers stabilizes them and improves their biopharmaceutical properties. In summary, this article illustrates the use of native chemical ligation technology in the cyclization of cyclotides, sunflower trypsin inhibitor-1, and conotoxins in our laboratory.
© 2010 Wiley Periodicals, Inc.
Keyword Cyclotides
Cyclic peptides
Cystine knot
Kalata B1
Alpha-conotoxin MII
3-dimensional solution structure
Macrocyclic trypsin-inhibitor
Cyclotide cycloviolacin O2
Birk protease inhibitors
Polypeptide kalata B1
Backbone cyclization
Plant cyclotides
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Special Issue Dedicated to the 2009 Bruce Merrifield Award Winner Stephen B. H. Kent. Published under "Invited Review".

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 49 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 18 Jul 2010, 00:09:40 EST