Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Molecular insights into the AT1 antagonism based on biophysical and in silico studies of telmisartan
Δημιουργός/Συγγραφέας:	Kritsi E. Potamitis C. Durdagi S. [EL] Ζουμπουλάκης, Παναγιώτης[EN] Zoumpoulakis, Panagiotis Golic Grdadolnik S. [EL] Μαυρομούστακος, Θωμάς[EN] Mavromoustakos, Thomas
Ημερομηνία:	2013
Γλώσσα:	Αγγλικά
ISSN:	1054-2523
DOI:	10.1007/s00044-012-0464-5
Περίληψη:	AT1 antagonists (SARTANs) constitute one of the most successful classes of antihypertensive agents. These molecules interfere with the renin angiotensin system by preventing the vasoconstrictive hormone angiotensin II from binding onto the AT1 receptor. It is proposed that SARTANs exert their biological action by inserting into the lipid membrane and then diffuse to the active site of AT1 receptor. In this article, the conformational properties of telmisartan are analyzed both in solution and in the active site of the AT1 receptor using conformational analysis, molecular docking, Molecular Dynamics (MD) simulations, and in silico Ala-scanning mutagenesis studies. Combined results reveal telmisartan's crucial structural characteristics and classify the importance of receptor's amino acids for ligand binding. Since telmisartan is exerting its activity on a transmembrane receptor, Differential Scanning Calorimetry was applied to study the drug effects in lipid bilayers mimicking the biological membrane environment. Of paramount importance, is the finding that telmisartan exerted similarities but also significant differences with other AT1 antagonists on the basis of their interaction with lipid bilayers and subsequent docking into the active site. This could in part explain their similar mode of action and in parallel their distinct pharmacological profile.
Τίτλος πηγής δημοσίευσης:	Medicinal Chemistry Research
Τόμος/Κεφάλαιο:	22
Τεύχος:	10
Σελίδες:	4842-4857
Θεματική Κατηγορία:	[EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	AT1 antagonists Conformational analysis DSC MD simulations Molecular docking Sartans Telmisartan
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2013 Springer Science+Business Media New York.
Σημειώσεις:	Seventh Framework Programme, FP7: 245866, FP7-REGPOT-2009-1
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο