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 Citations (Scopus)

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
StatePublished - Dec 2 1997

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Tics
Bioassay
Dipeptides
Opioid Receptors
Bioactivity
Opioid Analgesics
Conformations
Biological Assay

ASJC Scopus subject areas

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

Cite this

Liao, S., Lin, J., Shenderovich, M. D., Han, Y., Hasohata, K., Davis, P., ... Hruby, V. J. (1997). The stereochemical requirements of the novel δ-opioid selective dipeptide antagonist TMT-Tic. Bioorganic and Medicinal Chemistry Letters, 7(23), 3049-3052.

The stereochemical requirements of the novel δ-opioid selective dipeptide antagonist TMT-Tic. / Liao, Subo; Lin, Jun; Shenderovich, Mark D.; Han, Yinglin; Hasohata, Keiko; Davis, Peg; Qiu, Wei; Porreca, Frank; Yamamura, Henry I.; Hruby, Victor J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 7, No. 23, 02.12.1997, p. 3049-3052.

Research output: Contribution to journalArticle

Liao, S, Lin, J, Shenderovich, MD, Han, Y, Hasohata, K, Davis, P, Qiu, W, Porreca, F, Yamamura, HI & Hruby, VJ 1997, 'The stereochemical requirements of the novel δ-opioid selective dipeptide antagonist TMT-Tic', Bioorganic and Medicinal Chemistry Letters, vol. 7, no. 23, pp. 3049-3052.
Liao S, Lin J, Shenderovich MD, Han Y, Hasohata K, Davis P et al. The stereochemical requirements of the novel δ-opioid selective dipeptide antagonist TMT-Tic. Bioorganic and Medicinal Chemistry Letters. 1997 Dec 2;7(23):3049-3052.
Liao, Subo ; Lin, Jun ; Shenderovich, Mark D. ; Han, Yinglin ; Hasohata, Keiko ; Davis, Peg ; Qiu, Wei ; Porreca, Frank ; Yamamura, Henry I. ; Hruby, Victor J. / The stereochemical requirements of the novel δ-opioid selective dipeptide antagonist TMT-Tic. In: Bioorganic and Medicinal Chemistry Letters. 1997 ; Vol. 7, No. 23. pp. 3049-3052.
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