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

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

Volume: 23 Issue: 1

Author(s): Tahsin F. Kellici, Dimitrios Ntountaniotis, Eftichia Kritsi, Maria Zervou, Panagiotis Zoumpoulakis, Constantinos Potamitis, Serdar Durdagi, Ramin Ekhteiari Salmas, Gizem Ergun, Ebru Gokdemir, Maria Halabalaki, Ioannis P. Gerothanassis, George Liapakis, Andreas Tzakos and Thomas Mavromoustakos

Affiliation:

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

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.

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Kellici F. Tahsin, Ntountaniotis Dimitrios, Kritsi Eftichia, Zervou Maria, Zoumpoulakis Panagiotis, Potamitis Constantinos, Durdagi Serdar, Salmas Ekhteiari Ramin, Ergun Gizem, Gokdemir Ebru, Halabalaki Maria, Gerothanassis P. Ioannis, Liapakis George, Tzakos Andreas and Mavromoustakos Thomas, Leveraging NMR and X-ray Data of the Free Ligands to Build Better Drugs Targeting Angiotensin II Type 1 G-Protein Coupled Receptor, Current Medicinal Chemistry 2016; 23 (1) . https://dx.doi.org/10.2174/0929867323666151117122116