Synthesis of carboxyl-terminal extension analogs of dermorphin and evaluation of their opioid receptor-binding and opioid activities.
Eight dermorphin (DM) analogs extended at the C-terminus, based on the sequence of prepro-DM deduced from the cDNA, were synthesized by a simultaneous solid-phase method in which a pair of peptides was synthesized in a single vessel. Six peptides (three pairs) were obtained in satisfactory yields (17-37%). In the opioid receptor-binding assay using a rat brain homogenate, the mu-affinities correlated well to the net positive charges of peptides, and DM-Gly-Glu-Ala-Lys-Lys-Ile-Lys-Arg-NH2 showed the highest mu-affinity, 115-fold that of DM. But, in the guinea pig ileum assay, extension analogs with net positive charge of 2 to 4 exhibited potencies comparable to or slightly lower than that of DM, even though they possessed 2- to 115-fold higher mu-affinities than DM in the receptor-binding assay.
Ambo
A
A
Tohoku College of Pharmacy, Sendai, Japan.
Sasaki
Y
Y
Suzuki
K
K
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D004353:Drug Evaluation, Preclinical; D004723:Endorphins / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D018847:Opioid Peptides; D011957:Receptors, Opioid / Q000378:metabolism*
D000701:Analgesics, Opioid; D004723:Endorphins; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; C030058:dermorphin