Utlra-stable peptide scaffolds for protein engineering synthesis and folding of the circular cystine knotted cyclotide cycloviolacin O2

Aboye, T, Clark, Richard J., Craik, David J. and Goransson, U (2008) Utlra-stable peptide scaffolds for protein engineering synthesis and folding of the circular cystine knotted cyclotide cycloviolacin O2. ChemBioChem, 9 1: 103-113. doi:10.1002/cbic.200700357


Author Aboye, T
Clark, Richard J.
Craik, David J.
Goransson, U
Title Utlra-stable peptide scaffolds for protein engineering synthesis and folding of the circular cystine knotted cyclotide cycloviolacin O2
Journal name ChemBioChem   Check publisher's open access policy
ISSN 1439-7633
Publication date 2008-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1002/cbic.200700357
Open Access Status Not yet assessed
Volume 9
Issue 1
Start page 103
End page 113
Total pages 10
Editor Alan R. Fersht
Place of publication Weinheim, Germany
Publisher Wiley
Language eng
Subject C1
970103 Expanding Knowledge in the Chemical Sciences
030406 Proteins and Peptides
Abstract The cyclic cystine knot motif as defined by the cyclotide peptide family, is an attractive scaffold for protein engineering. To date, however, the utilisotion of this scaffold has been limited by the inability to synthesise members of the most diverse and biologically active subfamily, the bracelet cyclotides. This study describes the synthesis and first direct oxidative folding of a bracelet cyclotide-cycloviolacin O2-and thus provides on efficient method for exploring the most potent cyclic cystine knot peptides. The linear chain of cycloviolacin O2 was assembled by solid-phase Fmoc peptide synthesis and cyclised by thioester-mediated native chemical ligation, and the inherent difficulties of folding bracelet cyclotides were successfully overcome in a single-step reaction. The folding pathway was characterised and was found to include predominating fully oxidised intermediates that slowly converted to the native peptide structure.
Keyword Biochemistry & Molecular Biology
Chemistry, Medicinal
Biochemistry & Molecular Biology
Pharmacology & Pharmacy
BIOCHEMISTRY & MOLECULAR BIOLOGY
CHEMISTRY, MEDICINAL
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: 2009 Higher Education Research Data Collection
 
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Created: Thu, 16 Apr 2009, 19:53:57 EST by Jennifer Greder on behalf of Institute for Molecular Bioscience