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

Takashi Yamamoto, Padma Nair, Shou wu Ma, Peg Davis, Henry I. Yamamura, Todd W Vanderah, Frank Porreca, Josephine Lai, Victor J Hruby

Research output: Contribution to journalArticle

24 Citations (Scopus)

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′-(CF3)2Bzl]), 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′-(CF3)2Bzl]) was found as a highly selective δ opioid agonist over μ receptor in conventional tissue-based assays, together with an effective NK1 antagonist activity and good metabolic stability with more than 24 h half life in rat plasma.

Original languageEnglish (US)
Pages (from-to)7337-7343
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number20
DOIs
StatePublished - Oct 15 2009

Fingerprint

Neurokinin-1 Receptor Antagonists
Neurokinin-1 Receptors
Cystine
Opioid Peptides
Opioid Receptors
Bioactivity
Opioid Analgesics
Half-Life
Lead compounds
Rats
Assays
Tissue
Plasmas
Lead

Keywords

  • Bifunctional compounds
  • Disulfide bond
  • Metabolic stability
  • Multivalent ligands
  • Neutokinin-1 antagonists
  • Opioid agonists

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

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; Nair, Padma; Ma, Shou wu; Davis, Peg; Yamamura, Henry I.; Vanderah, Todd W; Porreca, Frank; Lai, Josephine; Hruby, Victor J.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 20, 15.10.2009, p. 7337-7343.

Research output: Contribution to journalArticle

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AU - Yamamura, Henry I.

AU - Vanderah, Todd W

AU - Porreca, Frank

AU - Lai, Josephine

AU - Hruby, Victor J

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