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Lookup NU author(s): Professor William Clegg, Dr Mark Elsegood
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The recently isolated broad-spectrum antiparasitic apicidin (1) is one of the few naturally occurring cyclic tetrapeptides (CTP). Depending on the solvent, the backbone of 1 exhibits two γ-turns (in CH2Cl2) or a β-turn (in DMSO), differing solely in the rotation of the plane of one of the amide bonds. In the X-ray crystal structure, the peptidic C=Os and NHs are on opposite sides of the backbone plane, giving rise to infinite stacks of cyclotetrapeptides connected by three intermolecular hydrogen bonds between the backbones. Conformational searches (Amber force field) on a truncated model system of 1 confirm all three backbone conformations to be low-energy states. The previously synthesized analogs of 1 containing a reduced amide bond exhibit the same backbone conformation as 1 in DMSO, which is confirmed further by the X-ray crystal structure of a model system of the desoxy analogs of 1. This similarity helps in explaining why the desoxy analogs retain some of the antiprotozoal activities of apicidin. The backbone-reduction approach designed to facilitate the cyclization step of the acyclic precursors of the CTPs seems to retain the conformational preferences of the parent peptide backbone, Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.
Author(s): Kranz M, Murray PJ, Taylor S, Upton RJ, Clegg W, Elsegood MRJ
Publication type: Article
Publication status: Published
Journal: Journal of Peptide Science
Year: 2006
Volume: 12
Issue: 6
Pages: 383-388
ISSN (print): 1075-2617
ISSN (electronic): 1099-1387
Publisher: John Wiley & Sons Ltd.
URL: http://dx.doi.org/10.1002/psc.738
DOI: 10.1002/psc.738
PubMed id: 16342331
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