Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Thermal, dynamic and structural properties of drug AT(1) antagonist olmesartan in lipid bilayers
Δημιουργός/Συγγραφέας:	Ntountaniotis, Dimitrios Mali, Gregor Grdadolnik, Simona Golic Maria, Halabalaki Skaltsounis, Alexios-Leandros Potamitis, Constantinos [EL] Σιάπη, Ελένη[EN] Siapi, Eleni Chatzigeorgiou, Petros Rappolt, Michael [EL] Μαυρομούστακος, Θωμάς[EN] Mavromoustakos, Thomas
Εκδότης:	Elsevier BV
Τόπος έκδοσης:	AMSTERDAM
Ημερομηνία:	2011-12
Γλώσσα:	Αγγλικά
ISSN:	0005-2736
DOI:	10.1016/j.bbamem.2011.08.001
Περίληψη:	It is proposed that AT(1) antagonists (ARBs) exert their biological action by inserting into the lipid membrane and then diffuse to the active site of AT(1) receptor. Thus, lipid bilayers are expected to be actively involved and play a critical role in drug action. For this reason, the thermal, dynamic and structural effects of olmesartan alone and together with cholesterol were studied using differential scanning calorimetry (DSC), C-13 magic-angle spinning (MAS) nuclear magnetic resonance (NMR), cross-polarization (UP) MAS NMR, and Raman spectroscopy as well as small- and wide angle X-ray scattering (SAXS and WAXS) on dipalmitoyl-phosphatidylcholine (DPPC) multilamellar vesicles. C-13 CP/MAS spectra provided direct evidence for the incorporation of olmesartan and cholesterol in lipid bilayers. Raman and X-ray data revealed how both molecules modify the bilayer's properties. Olmesartan locates itself at the head-group region and upper segment of the lipid bilayers as C-13 CP/MAS spectra show that its presence causes significant chemical shift changes mainly in the A ring of the steroidal part of cholesterol. The influence of olmesartan on DPPC/cholesterol bilayers is less pronounced. Although, olmesartan and cholesterol are residing at the same region of the lipid bilayers, due to their different sizes, display distinct impacts on the bilayer's properties. Cholesterol broadens significantly the main transition, abolishes the pre-transition, and decreases the membrane fluidity above the main transition. Olmesartan is the only so far studied ARB that increases the gauche:trans ratio in the liquid crystalline phase. These significant differences of olmesartan may in part explain its distinct pharmacological profile.
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:	1808
Τεύχος:	12
Σελίδες:	2995-3006
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General) [EL] Φυσική[EN] Physics
Λέξεις-Κλειδιά:	Olmesartan Dipalmitoyl-phosphatidylcholine bilayer Small-angle and wide angle X-ray scattering Raman spectroscopy Differential scanning calorimetry Solid state NMR spectroscopy Biophysics
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2011 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