Abstract

The angiotensin II type 1 receptor (AT₁R) has been recently crystallized. A new era has emerged for the structure-based rational drug design and the synthesis of novel AT₁R antagonists. In this critical review, the X-ray crystallographic data of commercially available AT₁R antagonists in free form are analyzed and compared with the conformational analysis results obtained using a combination of NMR spectroscopy and Molecular Modeling. The same AT₁R antagonists are docked and compared in terms of their interactions in their binding site using homology models and the crystallized AT₁R receptor. Various aspects derived from these comparisons regarding rational drug design are outlined.

Keywords: Angiotensin II type 1 receptor antagonists, conformational analysis, NMR, molecular modeling, sartans, X-ray, GPCR, AT₁R.