Conformational sampling of bioactive conformers: a low-temperature NMR study of 15N-Leu-enkephalin.
J Pept Sci
; 4(4): 253-65, 1998 Jun.
Article
em En
| MEDLINE
| ID: mdl-9680059
ABSTRACT
Conformational studies of enkephalins are hampered by their high flexibility which leads to mixtures of quasi-isoenergetic conformers in solution and makes NOEs very difficult to detect in NMR spectra. In order to improve the quality of the NMR data, Leu-enkephalin was synthesized with 15N-labelled uniformly on all amide nitrogens and examined in a viscous solvent medium at low temperature. HMQC NOESY spectra of the labelled Leu-enkephalin in a DMSOd6/H2O) mixture at 275 K do show numerous NOEs, but these are not consistent with a single conformer and are only sufficient to describe the conformational state as a mixture of several conformers. Here a different approach to the structure-activity relationships of enkephalins is presented it is possible to analyse the NMR data in terms of limiting canonical structures (i.e. beta- and gamma-turns) and finally to select only those consistent with the requirements of delta selective agonists and antagonists. This strategy results in the prediction of a family of conformers that may be useful in the design of new delta selective opioid peptides.
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Base de dados:
MEDLINE
Assunto principal:
Conformação Proteica
/
Encefalina Leucina
/
Espectroscopia de Ressonância Magnética
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article