Examination of the conformational meaning of "delta-address" in the dermenkephalin sequence.
Comprehensive energy calculations were applied to four opioid-related peptides with different receptor selectivities, namely the delta-selective dermenkephalin (Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2, DRE), the mu-selective dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, DRM) and their "hybrid" peptides DRM/DRE (Tyr-D-Ala-Phe-Gly-Leu-Met-Asp-NH2) and DRE/DRM (Tyr-D-Met-Phe-His-Tyr-Pro-Ser-NH2). It was shown that the N-terminal tripeptide "mu-messages" in the delta-selective ligands DRE and DRM/DRE can possess similar low energy space arrangements of their functionally important elements (the N-terminal alpha-amino group and the aromatic moieties of Tyr and Phe), but that these are different from the space arrangement of these moieties in mu-selective DRM and DRE/DRM. These results suggest that the C-terminal tripeptide "delta-address" in DRE may influence the conformation of the "mu-message" in DRM. A refined model for the delta-receptor-bound conformation of DRE is proposed based on these calculations which is similar to that previously suggested for the cyclic delta-selective peptide [D-Pen2, D-Pen5]enkephalin (DPDPE). This model also has partial correspondence with the structure of the delta-selective alkaloid naltrindole.
Nikiforovich
G V
GV
Department of Chemistry, University of Arizona, Tucson 85721.
Hruby
V J
VJ
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000737:chemistry*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D018847:Opioid Peptides; D011487:Protein Conformation; D011957:Receptors, Opioid / Q000378:metabolism; D017450:Receptors, Opioid, mu; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C054178:dermorphin receptor; C059567:deltorphin; C030058:dermorphin