Author/Authors :
Subo Liao، نويسنده , , Jun Lin، نويسنده , , Mark D. Shenderovich، نويسنده , , Yinglin Han، نويسنده , , Keiko Hasohata، نويسنده , , Peg Davis، نويسنده , , Wei Qiu، نويسنده , , Frank Porreca، نويسنده , , Henry I. Yamamura، نويسنده , , Victor J. Hruby، نويسنده ,
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.
