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Solution structure determination of oligoureas using methylene spin state selective NMR at 13 C natural abundance
Author(s) -
Guichard Gilles,
Violette Aude,
Chassaing Gérard,
Miclet Emeric
Publication year - 2008
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.2271
Subject(s) - chemistry , methylene , molecule , crystallography , nuclear magnetic resonance spectroscopy , proton nmr , stereochemistry , pulse sequence , computational chemistry , nuclear magnetic resonance , organic chemistry , physics
Ability of N , N ′‐linked oligoureas containing proteinogenic side chains to adopt a stable helix conformation in solution has been described recently. NMR as well as circular dichroism (CD) spectroscopies were employed to gain insight into their specific fold. It is herein proposed to extend the structural information available on these peptidomimetics by an advantageous use of a methylene spin state selective NMR experiment. Homodecoupling provided by the pulse scheme made it possible to readily measure conformation‐dependent 3 J HH constants that are difficult if not impossible to obtain with standard NMR experiments. Adding those couplings to the NMR restraints improved the quality of the structure calculations significantly, as judged by a ca 30% decrease of the root mean square deviation (RMSD) obtained over an ensemble of 20 structures. Moreover, accurate determination of individual 1 J CH couplings within each methylene group revealed uniform values throughout the oligourea sequence, with 1 J CH systematically slightly larger for the pro‐S hydrogen than for the pro‐R . As shown in this study, the methylene spin state selective NMR experiment displays a good intrinsic sensitivity and could therefore provide valuable structural information at 13 C natural abundance for peptidomimetic molecules and foldamers bearing diastereotopic methylene protons. Copyright © 2008 John Wiley & Sons, Ltd.