PT  - JOURNAL ARTICLE
AU  - Loew, G
AU  - Keys, C
AU  - Luke, B
AU  - Polgar, W
AU  - Toll, L
TI  - Structure-activity studies of morphiceptin analogs: receptor binding and molecular determinants of mu-affinity and selectivity.
DP  - 1986 Jun 01
TA  - Molecular Pharmacology
PG  - 546--553
VI  - 29
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/29/6/546.short
4100  - http://molpharm.aspetjournals.org/content/29/6/546.full
SO  - Mol Pharmacol1986 Jun 01; 29
AB  - 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.