Racemic and quasi-racemic x-ray structures of cyclic disulfide-rich peptide drug scaffolds

Wang, Conan K., King, Gordon J., Northfield, Susan E., Ojeda, Paola G. and Craik, David J. (2014) Racemic and quasi-racemic x-ray structures of cyclic disulfide-rich peptide drug scaffolds. Angewandte Chemie - International Edition, 53 42: 11236-11241. doi:10.1002/anie.201406563

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Author Wang, Conan K.
King, Gordon J.
Northfield, Susan E.
Ojeda, Paola G.
Craik, David J.
Title Racemic and quasi-racemic x-ray structures of cyclic disulfide-rich peptide drug scaffolds
Journal name Angewandte Chemie - International Edition   Check publisher's open access policy
ISSN 1433-7851
Publication date 2014-10-13
Year available 2014
Sub-type Article (original research)
DOI 10.1002/anie.201406563
Open Access Status File (Author Post-print)
Volume 53
Issue 42
Start page 11236
End page 11241
Total pages 6
Place of publication Weinheim, Germany
Publisher Wiley
Language eng
Subject 1503 Catalysis
1600 Chemistry
Abstract Cyclic disulfide-rich peptides have exceptional stability and are promising frameworks for drug design. We were interested in obtaining X-ray structures of these peptides to assist in drug design applications, but disulfide-rich peptides can be notoriously difficult to crystallize. To overcome this limitation, we chemically synthesized the L- and D-forms of three prototypic cyclic disulfide-rich peptides: SFTI-1 (14-mer with one disulfide bond), cVc1.1 (22-mer with two disulfide bonds), and kB1 (29-mer with three disulfide bonds) for racemic crystallization studies. Facile crystal formation occurred from a racemic mixture of each peptide, giving structures solved at resolutions from 1.25 Å to 1.9 Å. Additionally, we obtained the quasi-racemic structures of two mutants of kB1, [G6A]kB1, and [V25A]kB1, which were solved at a resolution of 1.25 Å and 2.3 Å, respectively. The racemic crystallography approach appears to have broad utility in the structural biology of cyclic peptides.
Keyword Crystal structures
Cyclic peptides
D-amino acids
Disulfide bonds
Racemic crystallography
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
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