Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Interactions of the AT(1) antagonist valsartan with dipalmitoyl-phosphatidylcholine bilayers
Δημιουργός/Συγγραφέας:	Potamitis, C. Chatzigeorgiou, P. [EL] Σιάπη, Ελένη[EN] Siapi, Eleni Viras, K. [EL] Μαυρομούστακος, Θωμάς[EN] Mavromoustakos, Thomas Hodzic, A. Pabst, G. Cacho-Nerin, F. Laggner, P. Rappolt, M.
Εκδότης:	Elsevier BV
Τόπος έκδοσης:	AMSTERDAM
Ημερομηνία:	2011-06
Γλώσσα:	Αγγλικά
ISSN:	0005-2736
DOI:	10.1016/j.bbamem.2011.02.002
Περίληψη:	Valsartan is a marketed drug with high affinity to the type 1 angiotensin (AT(1)) receptor. It has been reported that AT(1) antagonists may reach the receptor site by diffusion through the plasma membrane. For this reason we have applied a combination of differential scanning calorimetry (DSC). Raman spectroscopy and small and wide angle X-ray scattering (SAXS and WAXS) to investigate the interactions of valsartan with the model membrane of dipalmitoyl-phosphatidylcholine (DPPC). Hence, the thermal, dynamic and structural effects in bulk as well as local dynamic properties in the bilayers were studied with different valsartan concentrations ranging from 0 to 20 mol%. The DSC experimental results showed that valsartan causes a lowering and broadening of the phase transition. A splitting of the main transition is observed at high drug concentrations. In addition, valsartan causes an increase in enthalpy change of the main transition, which can be related to the induction of interdigitation of the lipid bilayers in the gel phase. Raman spectroscopy revealed distinct interactions between valsartan with the lipid interface localizing it in the polar head group region and in the upper part of the hydrophobic core. This localization of the drug molecule in the lipid bilayers supports the interdigitation view. SAXS measurements confirm a monotonous bilayer thinning in the fluid phase, associated with a steady increase of the root mean square fluctuation of the bilayers as the valsartan concentration is increased. At high drug concentrations these fluctuations are mainly governed by the electrostatic repulsion of neighboring membranes. Finally, valsartans' complex thermal and structural effects on DPPC bilayers are illustrated and discussed on a molecular level.
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:	6
Σελίδες:	1753-1763
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General) [EL] Φυσική[EN] Physics
Λέξεις-Κλειδιά:	Valsartan Dipalmitoyl-phosphatidylcholine Bilayer Small-angle and wide-angle X-ray scattering Raman spectroscopy Differential scanning calorimetry 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