Leveraging NMR and X-ray Data of the Free Ligands to Build Better Drugs Targeting Angiotensin II Type 1 G-Protein Coupled Receptor

• Published in: Current medicinal chemistry Vol. 23; no. 1; p. 36
• Main Authors: Kellici, Tahsin F, Ntountaniotis, Dimitrios, Kritsi, Eftichia, Zervou, Maria, Zoumpoulakis, Panagiotis, Potamitis, Constantinos, Durdagi, Serdar, Salmas, Ramin Ekhteiari, Ergun, Gizem, Gokdemir, Ebru, Halabalaki, Maria, Gerothanassis, Ioannis P, Liapakis, George, Tzakos, Andreas, Mavromoustakos, Thomas
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-01-2016
• Subjects: Angiotensin II Type 1 Receptor Blockers - chemistry; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Crystallography, X-Ray - methods; Drug Discovery - methods; Humans; Ligands; Magnetic Resonance Spectroscopy - methods; Molecular Docking Simulation; Receptor, Angiotensin, Type 1 - chemistry; Receptor, Angiotensin, Type 1 - metabolism
• ISSN: 1875-533X
• DOI: 10.2174/0929867323666151117122116

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.