The rotamer populations around the C-a-C-F bond of amino acid residues with one B-proton can be calculated from homonuclear and heteronuclear vicinal coupling constants. The measurement of long-range heteronuclear coupling constants, however, suffers from the inherent low sensitivity of the heteronuclear multiple bond experiments. In this paper it is demonstrated that z-filtered homonuclear and heteronuclear relay spectroscopy provides a sensitive and accurate means for the evaluation of conformationally important vicinal coupiing constants. Sidechain conformations of the four stereoisomers of 8-rnethylphenylalanine residues in synthetic octapeptide analogues of CCK-8 were derived from the measured coupling constants. This information is not easily available from conformationai analysis based on simple steric considerations.
The cholecystokinin (26-33) [CCK (26-33)] octapeptide analog Asp-Tyr-D-Phe-Gly-Trp(N-Me)-Nle-Asp-Phe-NH2 (SNF 9007) is a potent and selective ligand for both the CCK-B and delta-opioid receptors. Pharmacological studies of SNF 9007 suggest a relationship between the ligand requirements of CCK-B and delta-opioid receptors, which further implies a possible structural relationship between these receptors. We have utilized topographical constrainment of the important Trp30 residue to investigate structural features of SNF 9007 that would distinguish between binding requirements in this region for the CCK-B and delta-opioid receptors. Thus, the four optically pure isomers of beta-MeTrp were substituted for L-Trp30 of SNF 9007. Receptor binding results suggest that the preferred topography of the Trp30 residue for CCK-B receptor binding may be the 2S,3S (erythro-L) configuration whereas for the delta-opioid receptor it may be the 2S,3R (threo-L) configuration. Molecular modeling studies of these ligands further support the recently revised receptor-bound model for CCK-B octapeptide ligands (Kolodziej et al. J. Med. Chem. 1995, 38, 137-149) and are in good agreement with the DPDPE-delta opioid receptor "template" model (Nikiforovich et al. Biopolymers 1991, 31, 941-955).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.