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

doi:10.1016/S0960-894X(97)10145-7

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 journal › Article › peer-review

33 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 language	English (US)
Pages (from-to)	3049-3052
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	7
Issue number	23
DOIs	https://doi.org/10.1016/S0960-894X(97)10145-7
State	Published - Dec 2 1997

ASJC Scopus subject areas

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

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10.1016/S0960-894X(97)10145-7

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title = "The stereochemical requirements of the novel δ-opioid selective dipeptide antagonist TMT-Tic",

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.",

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

note = "Funding Information: Acknowledgment: The authors acknowledge the financial support of grants from NIDA DA 06284 and the U.S. Public Health Service DK 17420, the Dean's Fellowship from the Grad. College of the University of Arizona for S.L., and the financial support from Yunnan Provincial Education Committee, P.R.C. for J.L. as a visiting scholar in the U.S.A. The contents are the responsibility of the authors and do not necessarily represent the official views of the USPHS.",

year = "1997",

month = dec,

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doi = "10.1016/S0960-894X(97)10145-7",

language = "English (US)",

volume = "7",

pages = "3049--3052",

journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - The stereochemical requirements of the novel δ-opioid selective dipeptide antagonist TMT-Tic

AU - Liao, Subo

AU - Lin, Jun

AU - Shenderovich, Mark D.

AU - Han, Yinglin

AU - Hasohata, Keiko

AU - Davis, Peg

AU - Qiu, Wei

AU - Porreca, Frank

AU - Yamamura, Henry I.

AU - Hruby, Victor J.

N1 - Funding Information: Acknowledgment: The authors acknowledge the financial support of grants from NIDA DA 06284 and the U.S. Public Health Service DK 17420, the Dean's Fellowship from the Grad. College of the University of Arizona for S.L., and the financial support from Yunnan Provincial Education Committee, P.R.C. for J.L. as a visiting scholar in the U.S.A. The contents are the responsibility of the authors and do not necessarily represent the official views of the USPHS.

PY - 1997/12/2

Y1 - 1997/12/2

N2 - 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.

AB - 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.

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U2 - 10.1016/S0960-894X(97)10145-7

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 23

ER -

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

Abstract

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