Conformational characteristics of receptor-selective opioid peptides. 1H n.m.r. and c.d. spectroscopic studies of delta-kephalin and [Val4]morphiceptin.
An investigation on the conformations of highly receptor-selective opioid peptides was carried out to gain further understanding of the structure-activity relationship of endogenous enkephalins. The preferred conformations of a highly mu-selective [Val4]morphiceptin and a highly delta-selective delta-kephalin have been probed by 1H n.m.r. solvent-, concentration- and temperature-dependences of amide protons to take the folded conformations stabilized by an intramolecular hydrogen bond and the anti-parallely extended dimeric structures respectively. Their possible stereo-conformations were proposed, based on the analyses of the vicinal coupling constants (JHNC alpha H). The conformational difference between the mu- and delta-selective opioid peptides was further ascertained by the c.d. measurements. The c.d. spectra of the mu-selective peptides show negative bands in the range of 210-230 nm, while those of the delta-selective ones show the opposite positive bands. A correlation between c.d. spectra and receptor-selectivity was possible.
Doi
M
M
Osaka University of Pharmaceutical Sciences, Japan.
Tanaka
M
M
Ikuma
K
K
Nabae
M
M
Kitamura
K
K
Inoue
M
M
Ishida
T
T
D002942:Circular Dichroism; D004723:Endorphins; D004745:Enkephalins; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides; D011487:Protein Conformation; D011957:Receptors, Opioid; D012997:Solvents; D013696:Temperature
D004723:Endorphins; D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D012997:Solvents; C037653:deltakephalin; C028889:morphiceptin