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Losartan's molecular basis of interaction with membranes and AT1 receptor.
Chemistry and Physics of Lipids ( IF 3.4 ) Pub Date : 2003-11-20 , DOI: 10.1016/s0009-3084(03)00053-7
P Zoumpoulakis 1 , I Daliani , M Zervou , I Kyrikou , E Siapi , G Lamprinidis , E Mikros , T Mavromoustakos
Affiliation  

Physicochemical methods were used to study the thermal and dynamic changes caused by losartan in the membrane bilayers. In addition, molecular modeling was implemented to explore its topography both in membranes and AT(1) receptor. Its incorporation resulted in the modification of thermal profile of dipalmitoyl phosphatidylcholine (DPPC) bilayers in a concentration dependent way up to 20mol% as it is depicted from the combination of differential scanning calorimetry (DSC) and MAS data. In particular, the presence of losartan caused lowering of the phase transition temperature and abolishment of the pretransition. T(1) experiments revealed the location of the drug into the membrane bilayers. The use of a combination of biophysical methods along with docking experiments brought out a possible two-step mechanism which involves incorporation of losartan at the interface of membrane bilayers and diffusion in the upper parts of AT(1) receptor helices IV-VII.

中文翻译:

氯沙坦与膜和AT1受体相互作用的分子基础。

物理化学方法用于研究氯沙坦在双层膜中引起的热和动态变化。此外,实施分子建模以探索其在膜和AT(1)受体中的形貌。如差示扫描量热法(DSC)和MAS数据的结合所描述的那样,其掺入导致二棕榈酰磷脂酰胆碱(DPPC)双层的热分布以浓度依赖性的方式改变,最高可达20mol%。特别地,氯沙坦的存在引起相转变温度的降低和预转变的取消。T(1)实验揭示了药物进入膜双层的位置。
更新日期:2019-11-01
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