Author/Authors :
Lawrence A. Reiter، نويسنده , , Christopher S. Jones، نويسنده , , William H. Brissette، نويسنده , , Sandra P. McCurdy، نويسنده , , Yuriy A. Abramov، نويسنده , , Jon Bordner، نويسنده , , Frank M. DiCapua، نويسنده , , Michael J. Munchhof، نويسنده , , Diane M. Rescek، نويسنده , , Ivan J. Samardjiev، نويسنده , , Jane M. Withka، نويسنده ,
Abstract :
The identification of small molecule modulators of biological processes mediated via protein–protein interactions has generally proved to be a challenging endeavor. In the case of the thrombopoietin receptor (TPOr), however, a number of small molecule types have been reported to display biological activity similar to that of the agonist protein TPO. Through a detailed analysis of structure–activity relationships, X-ray crystal structures, NMR coupling constants, nuclear Overhauser effects, and computational data, we have determined the agonism-inducing conformation of one series of small molecule TPOr agonists. The relationship of this agonism-inducing conformation to that of other series of TPO receptor agonists is discussed.
