Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/337366
Type: Artigo
Title: Combining nuclear magnetic resonance with molecular dynamics simulations to address sumatriptan interaction with model membranes
Author: Wood, Irene
Fabian, Lucas
Moglioni, Albertina
Fernando Cabeca, Luis
de Paula, Eneida
Pickholz, Monica
Abstract: The goal of this work is to obtain a complete map on the interactions between sumatriptan, an amphiphilic ionizable anti-migraine drug, with lipid bilayers. To this end, we combined two physico-chemical techniques-nuclear magnetic resonance and molecular dynamics simulations - to obtain a detailed picture at different pH values. Both approaches were used considering the strength and constraints of each one. NMR experiments were performed at pH 7.4 where at least 95% of the drug molecules are in their protonated state. From NMR, sumatriptan shows partition on the interfacial region of model membranes (near the head groups and intercalating between adjacent lipids), inducing changes in chemical environment and affecting lipid dynamics of liposomes, in a dose dependent manner. Due to the experimental instability of lipid bilayers at high pH, we took advantage of the molecular dynamics power to emulate different pH values, to simulate sumatriptan in bilayers including at fully uncharged state. Simulations show that the neutral species have preferential orientation within the bilayer interface while the distribution of protonated drugs is independent on the initial conditions. In summary, several properties depicted the interfacial partition of the anti-migraine drug at the water-lipid interface at different conditions. Both techniques were found complementary to shed light on the structural and dynamics of sumatriptan-lipid bilayer interactions
Subject: Dinâmica molecular
Country: Irlanda
Editor: Elsevier
Rights: Fechado
Identifier DOI: 10.1016/j.chemphyslip.2019.104792
Address: https://www.sciencedirect.com/science/article/pii/S0009308419300751
Date Issue: 2019
Appears in Collections:IB - Artigos e Outros Documentos

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