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Stabilization of an α‐helical conformation in an isolated hexapeptide inhibitor of calmodulin
Author(s) -
Esteve Vicent,
Blondelle Sylvie,
Celda Bernardo,
PérezPayá Enrique
Publication year - 2001
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/1097-0282(200112)59:7<467::aid-bip1052>3.0.co;2-5
Subject(s) - chemistry , calmodulin , nuclear magnetic resonance spectroscopy , stereochemistry , peptide , amino acid , circular dichroism , helix (gastropod) , glycine , alpha helix , oligopeptide , nuclear overhauser effect , peptide sequence , crystallography , calcium , biochemistry , organic chemistry , ecology , snail , biology , gene
The conformational properties of two hexapeptides, Ac‐LWRILW‐NH 2 and its D ‐amino acid counterpart Ac‐lwrilw‐NH 2 , identified as calmodulin inhibitors using mixture‐based synthetic combinatorial library approaches, have been characterised by NMR and CD spectroscopy. The peptides fold into an α‐helical conformation in aqueous solution. The observed short‐ and medium‐range nuclear Overhauser effects were consistent with the formation of an α‐helical structure and a reasonably well‐defined set of structures was obtained by using restraints from the NMR data in simulated annealing calculations. Analysis of glycine‐substitution analogues demonstrated that all the amino acids that make up the peptide sequence are important for the stabilization of the α‐helical conformation. The results suggest that a well‐defined set of interactions is indispensable to allow α‐helix formation in this short hexapeptide. © 2001 John Wiley & Sons, Inc. Biopolymers 59: 467–476, 2001