The stereochemical requirements of the novel δ-opioid selective dipeptide antagonist TMT-Tic

Subo Liao, Jun Lin, Mark D. Shenderovich, Yinglin Han, Keiko Hasohata, Peg Davis, Wei Qiu, Frank Porreca, Henry I. Yamamura, Victor J. Hruby

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Five conformationally constrained dipeptide TMT-L-Tic analogues have been synthesized and evaluated for their bioactivity using in vitro bioassays. The most potent and selective analogue (2S,3R)-TMT-L-Tic showed 9 nM binding affinity and 4000-fold selectivity for the δ vs μ opioid receptor. The lowest-energy conformation of (2S,3R)-TMT-L-Tic is suggested to be bioactive one in which the X, torsional angle is trans for TMT and gauche (+) for Tic.

Original languageEnglish (US)
Pages (from-to)3049-3052
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume7
Issue number23
DOIs
StatePublished - Dec 2 1997

ASJC Scopus subject areas

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

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