Interactions of antimalarials with the ion channel model MVP

• Grant number: 14/09299-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: July 30, 2014
• End date: July 29, 2015
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Antonio José da Costa Filho
• Grantee: Rafael Pianca Barroso
• Supervisor: Eduardo Arturo Perozo
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Chicago, United States
• Associated to the scholarship: 11/17155-1 - Interactions between pharmacologically-relevant molecules and model membranes: a molecular perspective, BP.PD

Abstract

This project presents a research proposal to obtain a BEPE grant associated with a postdoctoralfellowship (Proc. 2011/17155-1). The general goal of the ongoing PD project is a study of theinteractions between lipid model membranes and molecules presenting pharmacological interest. Yetpharmacological effect of many drugs is carried out through direct interaction with specific membrane-embedded target proteins. To gain further insights into these mechanisms we propose to directlyinvestigate drug interactions with a simplified ion channel model. These molecules are generallyrecognized as important drug targets in a variety of pathophysiological conditions. To reach ourobjectives we plan to learn and further develop the expression, purification and reconstitution in lipidmodel membranes of an archaeal hyperpolarization-activated potassium channel from Methanococcusjannaschii (MVP). This system will be subsequently used to investigate and characterize itsinteractions with amodiaquine and artesunate (two known antimalarial drugs). This study will bemainly based on Electron Paramagnetic Resonance (EPR) methods, including CW and pulsed EPRexperiments in combination/collaboration with electrophysiological measurements and X-raycrystallography. We expect that this collaborative project will ultimately broaden the expertise of our group in Brazil on those methodologies. (AU)