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

Article abstract of DOI:10.1016/S0960-894X(97)10145-7

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.