Conformational studies and receptor binding of delta selective opioid peptides.
Detailed energy-conformation studies of a linear (DTLET) and four cyclic (DPDPE, DPLPE, DPLCE,DCLPE), delta-selective opioid peptides were combined with computer assisted detailed receptor binding studies. The results of these studies have allowed the identification of a low energy conformer common to all of these analogs which could be responsible for their high affinity delta-receptor binding. This conformer contains multiple intramolecular H-bonds and is very different from the beta-II type structure previously postulated to lead to high affinity mu-receptor binding. This mu-binding conformer was found either to have higher energies or be greatly distorted in these delta selective analogs.
Keys
C
C
Life Sciences Division, SRI International, Menlo Park, California 94025.
Amsterdam
P
P
Payne
P
P
Toll
L
L
Loew
G
G
D000818:Animals; D001921:Brain / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D013329:Structure-Activity Relationship
D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta