Design of mu selective opioid dipeptide antagonists.
We have recently designed potent delta selective opioid antagonist dipeptides on the basis of a simple conformational analysis. Following a similar procedure we found a mu selective dipeptide antagonist, 2,6-dimethyl-Tyr-D-Phe-NH2. Although its selectivity is not as high as those of the quoted delta selective dipeptides it has good in vitro activity and looks very promising for further development since the 2,6-dimethyl-Tyr-D-Phe message, like the delta selective 2,6-dimethyl-Tyr-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid counterpart, seems able to impart antagonism to longer peptides.
Capasso
A
A
Dipartimento di Scienze Farmaceutiche, Università di Salerno, Italy.
Amodeo
P
P
Balboni
G
G
Guerrini
R
R
Lazarus
L H
LH
Temussi
P A
PA
Salvadori
S
S
D000818:Animals; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D009292:Narcotic Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D018847:Opioid Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004151:Dipeptides; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu