title: 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 (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.
authors.forename: Tahsin F
authors.initials: TF
authors.lastname: Kellici
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Ntountaniotis
authors.forename: Eftichia
authors.initials: E
authors.lastname: Kritsi
authors.forename: Maria
authors.initials: M
authors.lastname: Zervou
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Zoumpoulakis
authors.forename: Constantinos
authors.initials: C
authors.lastname: Potamitis
authors.forename: Serdar
authors.initials: S
authors.lastname: Durdagi
authors.forename: Ramin Ekhteiari
authors.initials: RE
authors.lastname: Salmas
authors.forename: Gizem
authors.initials: G
authors.lastname: Ergun
authors.forename: Ebru
authors.initials: E
authors.lastname: Gokdemir
authors.forename: Maria
authors.initials: M
authors.lastname: Halabalaki
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Gerothanassis
authors.forename: George
authors.initials: G
authors.lastname: Liapakis
authors.forename: Andreas
authors.initials: A
authors.lastname: Tzakos
authors.affiliation: Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece. tmavrom@chem.uoa.gr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D018360:Crystallography, X-Ray / Q000379:methods; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D062105:Molecular Docking Simulation; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D008024:Ligands; D044140:Receptor, Angiotensin, Type 1