Author/Authors :
Qiaolin Deng، نويسنده , , Jessica L. Frie، نويسنده , , Daria M. Marley، نويسنده , , Richard T. Beresis، نويسنده , , Ning Ren، نويسنده , , Tian-Quan Cai، نويسنده , , Andrew K.P. Taggart، نويسنده , , Kang Cheng، نويسنده , , Ester Carballo-Jane، نويسنده , , Junying Wang، نويسنده , , Xinchun Tong، نويسنده , , M. Gerard Waters، نويسنده , , James R. Tata، نويسنده , , Steven L. Colletti، نويسنده ,
Abstract :
A homology model of the nicotinic acid receptor GPR109A was constructed based on the X-ray crystal structure of bovine rhodopsin. An HTS hit was docked into the homology model. Characterization of the binding pocket by a grid-based surface calculation of the docking model suggested that a larger hydrophobic body plus a polar tail would improve interaction between the ligand and the receptor. The designed compounds were synthesized, and showed significantly improved binding affinity and activation of GPR109A.
