Five conformationally constrained dipeptide TMT-L-Tic analogues have b
een synthesized and evaluated for their bioactivity using in vitro bio
assays. The most potent and selective analogue (2S,SR)-TMT-L-Tic showe
d 9 nM binding affinity and 4000-fold selectivity for the delta vs mu
opioid receptor. The lowest-energy conformation of(2S,3R)-TMT-L-Tic is
suggested to be bioactive one in which the chi(1) torsional angle is
trans for TMT and gauche (+) for Tic. (C) 1997 Elsevier Science Ltd.