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

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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 χ1 torsional angle is trans for TMT and gauche (+) for Tic.

Five conformationally constrained dipeptide TMT-L-Tic analogues have been synthesized and evaluated using in vitro bioassays

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Permanent address: Department of Chemistry, Yunnan University, Kunming, P.R. China

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