The biological activity and metabolic stability of peptidic bifunctional compounds that are opioid receptor agonists and neurokinin-1 receptor antagonists with a cystine moiety.
In order to improve metabolic stability, a ring structure with a cystine moiety was introduced into TY027 (Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3',5'-(CF(3))(2)Bzl]), which is a lead compound of our developing bifunctional peptide possessing opioid agonist and NK1 antagonist activities. TY038 (Tyr-cyclo[D-Cys-Gly-Phe-Met-Pro-D-Cys]-Trp-NH-[3',5'-(CF(3))(2)Bzl]) was found as a highly selective delta opioid agonist over mu receptor in conventional tissue-based assays, together with an effective NK1 antagonist activity and good metabolic stability with more than 24h half life in rat plasma.
Yamamoto
Takashi
T
Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA.
Nair
Padma
P
Ma
Shou-wu
SW
Davis
Peg
P
Yamamura
Henry I
HI
Vanderah
Todd W
TW
Porreca
Frank
F
Lai
Josephine
J
Hruby
Victor J
VJ
D000818:Animals; D003553:Cystine / Q000737:chemistry*; D006207:Half-Life; D066298:In Vitro Techniques; D064729:Neurokinin-1 Receptor Antagonists; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011957:Receptors, Opioid / Q000819:agonists*
D064729:Neurokinin-1 Receptor Antagonists; D010455:Peptides; D011957:Receptors, Opioid; D003553:Cystine