TY - JOUR T1 - Structure-activity studies of morphiceptin analogs: receptor binding and molecular determinants of mu-affinity and selectivity. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 546 LP - 553 VL - 29 IS - 6 AU - G Loew AU - C Keys AU - B Luke AU - W Polgar AU - L Toll Y1 - 1986/06/01 UR - http://molpharm.aspetjournals.org/content/29/6/546.abstract N2 - In this study we report the systematic investigation of conformational profiles and electronic properties of a series of analogs of the mu-selective opioid peptide, morphiceptin, together with receptor-binding studies of some of these analogs. In particular, we have investigated the effect of: substitution in the second position, substitution of D-Pro for L-Pro in the second and fourth positions, the addition of an N-methyl group at the third position, and variations in the carboxyl end group. The binding studies confirm the preference of these analogs for mu- versus delta-receptor-binding sites and also indicate differences in mu-receptor affinity among them. The theoretical analyses allow identification of a preferred conformation leading to high mu-receptor affinity and two reliable indicators of relative mu-receptor affinities. These properties are the energy required to obtain the candidate mu-binding conformer and the extent to which each compound overlaps with the highest affinity compound in this conformation. In addition, electronic interactions deleterious to high affinity mu-binding are identified. ER -