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The biological activity and metabolic stability of peptidic bifunctional compounds that are opioid receptor agonists and neurokinin-1 receptor antagonists with a cystine moiety.

ABSTRACT: 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.

SUBMITTER: Yamamoto T

PROVIDER: S-EPMC2775479 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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The biological activity and metabolic stability of peptidic bifunctional compounds that are opioid receptor agonists and neurokinin-1 receptor antagonists with a cystine moiety.

Yamamoto Takashi T 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

Bioorganic & medicinal chemistry 20090821 20

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 N ...[more]

PMID: 19762245

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