Leveraging NMR and X-ray data of the free ligands to build better drugs targeting angiotensin II Type 1 G-Protein coupled receptor

Abstract

The angiotensin II type 1 receptor (AT<inf>1</inf>R) has been recently crystallized. A new era has emerged for the structure-based rational drug design and the synthesis of novel AT<inf>1</inf>R antagonists. In this critical review, the X-ray crystallographic data of commercially available AT<inf>1</inf>R 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 AT<inf>1</inf>R antagonists are docked and compared in terms of their interactions in their binding site using homology models and the crystallized AT<inf>1</inf>R receptor. Various aspects derived from these comparisons regarding rational drug design are outlined. © 2020 Elsevier B.V., All rights reserved.