Conformational sampling of bioactive conformers: a low-temperature NMR study of 15N-Leu–enkephalin

✍ Scribed by Pietro Amodeo; Fred Naider; Delia Picone; Teodorico Tancredi; Piero A. Temussi

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 277 KB
• Volume: 4
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/(sici)1099-1387(199806)4:4<253::aid-psc142>3.0.co;2-p

✦ Synopsis

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 15 N-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 DMSO d6 /H 2 O) 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. iand k-turns) and finally to select only those consistent with the requirements of l selective agonists and antagonists. This strategy results in the prediction of a family of conformers that may be useful in the design of new l selective opioid peptides.