Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Interactions at the bilayer interface and receptor site induced by the novel synthetic pyrrolidinone analog MMK3
Δημιουργός/Συγγραφέας:	Fotakis, C. Gega, S. [EL] Σιάπη, Ελένη[EN] Siapi, Eleni Potamitis, C. Viras, K. Moutevelis-Minakakis, P. Kokotos, C. G. Durdagi, S. Grdadolnik, S. Golic Sartori, B. Rappolt, M. [EL] Μαυρομούστακος, Θωμάς[EN] Mavromoustakos, Thomas
Εκδότης:	Elsevier BV
Τόπος έκδοσης:	AMSTERDAM
Ημερομηνία:	2010-03
Γλώσσα:	Αγγλικά
ISSN:	0005-2736
DOI:	10.1016/j.bbamem.2009.11.009
Περίληψη:	This work presents a thorough investigation of the interaction of the novel synthetic pyrrolidinone analog MMK3 with the model membrane system of dipalmitoylphosphatidylcholine (DPPC) and the receptor active site. MMK3 has been designed to exert anti hypertensive activity by functioning as an antagonist of the angiotensin 11 receptor of subtype 1 (AT(1)). Its low energy conformers were characterized by 2D rotating-frame Overhauser effect spectroscopy (ROESY) in combination with molecular dynamics (MD) simulations. Docking study of MMK3 shows that it fits to the AT, receptor as SARTANs, however, its biological activity appears to be lower. Thus, differential scanning calorimetry (DSC), Raman spectroscopy and small angle X-ray scattering (SAXS) experiments on the interaction of MMK3 with DPPC bilayers were carried out and results demonstrate that the drug is well incorporated into the membrane leaflets and furthermore causes partial bilayer interdigitation, although less effective than SARTANs. Thus, it appears that the nature of the bilayer matrix and the stereoelectronic active site requirements of the receptor are responsible for the low bioactivity of MMK3.
Τίτλος πηγής δημοσίευσης:	Biochimica Et Biophysica Acta (bba) - Biomembranes (formerly Part of Biochimica Et Biophysica Acta (bba) - Biophysics Including Photosynthesis) (incorporating Biochimica Et Biophysica Acta (bba) - Reviews on Biomembranes)
Τόμος/Κεφάλαιο:	1798
Τεύχος:	3
Σελίδες:	422-432
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General) [EL] Φυσική[EN] Physics
Λέξεις-Κλειδιά:	Partial interdigitation lipid bilayer MMK3 AT1 receptor Dipalmitoylphosphatidylcholine Biophysics
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2009 Elsevier B.V. All rights reserved.
Ηλεκτρονική διεύθυνση περιοδικού (link) :	http://www.elsevier.com/locate/bbamem
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Οργανικής και Φαρμακευτικής Χημείας (ΙΟΦΧ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο