Conformational features responsible for the binding of cyclic analogues of enkephalin to opioid receptors. III. Probable binding conformations of mu-agonists with phenylalanine in position 3.
Theoretical conformational analysis was carried out for several tetrapeptide analogues of beta-casomorphin and dermorphin containing a Phe residue in position 3. Sets of low-energy backbone structures of the mu-selective peptides [N-Me-Phe3, D-Pro4]-morphiceptin and Tyr-D-Orn-Phe-Asp-NH2 were obtained. These sets of structures were compared for geometrical similarity between themselves and with the low-energy conformations found for the delta-selective peptide Tyr-D-Cys-Phe-D-Pen-OH and nonactive peptide Tyr-Orn-Phe-Asp-NH2. Two pairs of geometrically similar conformations of mu-selective peptides, sharing no similarity with the conformations of peptides showing low affinity to the mu-receptor, were selected as two alternative models of probable mu-receptor-bound backbone conformations. Both models share geometrical similarity with the low-energy structures of the linear mu-selective peptide Tyr-D-Ala-Phe-Phe-NH2. Putative binding conformations of Tyr1 and Phe3 side chains are also discussed.
Shenderovich
M D
MD
Institute of Organic Synthesis, Latvian Academy of Sciences, Riga, Latvia, USSR.
Nikiforovich
G V
GV
Golbraikh
A A
AA
D000595:Amino Acid Sequence; D004723:Endorphins / Q000737:chemistry / Q000378:metabolism; D004745:Enkephalins / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D018847:Opioid Peptides; D010649:Phenylalanine; D011487:Protein Conformation; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D013329:Structure-Activity Relationship
D004723:Endorphins; D004745:Enkephalins; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C030058:dermorphin; D010649:Phenylalanine; C021968:beta-casomorphins; C044708:morphiceptin, N-Me-Phe(3)-