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).