Conformations of cyclic octapeptides and the influence of heterocyclic ring constraints upon calcium binding

Cusack, R. M., Grondahl, L., Abbenante, G., Fairlie, D. P., Gahan, L. R., Hanson, G. R. and Hambley, T. W. (2000) Conformations of cyclic octapeptides and the influence of heterocyclic ring constraints upon calcium binding. Journal of The Chemical Society-perkin Transactions 2, 2: 323-331. doi:10.1039/a906090a


Author Cusack, R. M.
Grondahl, L.
Abbenante, G.
Fairlie, D. P.
Gahan, L. R.
Hanson, G. R.
Hambley, T. W.
Title Conformations of cyclic octapeptides and the influence of heterocyclic ring constraints upon calcium binding
Journal name Journal of The Chemical Society-perkin Transactions 2   Check publisher's open access policy
ISSN 1470-1820
Publication date 2000-01-01
Sub-type Article (original research)
DOI 10.1039/a906090a
Issue 2
Start page 323
End page 331
Total pages 9
Editor S R Buxton
Place of publication Cambridge, UK
Publisher The Royal Society of Chemistry
Language eng
Subject 250000 Chemical Sciences
C1
250302 Biological and Medical Chemistry
780103 Chemical sciences
250204 Bioinorganic Chemistry
780105 Biological sciences
Abstract A comparison is made between the structures and calcium binding properties of four cyclic octapeptides that differ in the number of heterocyclic thiazole and oxazoline ring constraints. The conformations of the naturally occurring cyclic octapeptides ascidiacyclamide 1 and patellamide D 2, which each contain two oxazoline and two thiazole rings, are compared by H-1 NMR spectroscopy with the analogues cyclo(Thr-D-Val(Thz)-Ile)(2) 3 with just two thiazoles, and cyclo(Thr-D-Val-alpha Abu-Ile)(2) 4, with no 5-membered rings. The conformations observed in the solid state for ascidiacyclamide (saddle) and patellamide D (twisted figure of eight) were retained in solution, whilst peptide 3 was found to have a chair shape and peptide 4 displayed a range of conformations. The solid state structure of 4 revealed that the peptide takes a relatively planar conformation with a number of transannular hydrogen bonds, which are apparently retained in solution. Complexation studies utilising H-1 NMR and CD spectroscopy yielded 1∶1 calcium-peptide binding constants (log K) for the four peptides (2.9 (1), 2.8 (2), 4.0 (3) and 5.5 (4)) as well as a 1 : 2 metal-peptide binding constant for 3 (log K = 4.5). The affinity for Ca2+ thus decreases with increasing number of 5-membered ring constraints in the macrocycle (4 > 3 > 2 approximate to 1).
Keyword Chemistry, Organic
Chemistry, Physical
Ascidian Lissoclinum-patella
Crystal-structure
Ion-binding
Molecular-conformation
Circular-dichroism
Internal Mobility
Peptide
Complex
Ascidiacyclamide
Analog
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 13 Aug 2007, 21:34:20 EST