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Investigation of molecular mechanisms of action of chelating drugs on protein-lipid model membranes by X-ray fluorescence
Authors:N. N. Novikova  S. I. Zheludeva  M. V. Koval’chuk  N. D. Stepina  A. I. Erko  E. A. Yur’eva
Affiliation:(1) Molecular Therapeutics Laboratory, Program in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants' Hospital of RI, Alpert Medical School of Brown University, Providence, RI 02905, USA;(2) Division of Biology and Medicine, Brown University, Providence, RI 02912, USA
Abstract:Protein-lipid films based on the enzyme alkaline phosphatase were subjected to the action of chelating drugs, which are used for accelerating the removal of heavy metals from the human body, and the elemental composition of the resulting films was investigated. Total-reflection X-ray fluorescence measurements were performed at the Berlin Electron Storage Ring Company for Synchrotron Radiation (BESSY) in Germany. A comparative estimation of the protective effect of four drugs (EDTA, succimer, xydiphone, and mediphon) on membrane-bound enzymes damaged by lead ions was made. The changes in the elemental composition of the protein-lipid films caused by high doses of chelating drugs were investigated. It was shown that state-of-the-art X-ray techniques can, in principle, be used to develop new methods for the in vitro evaluation of the efficiency of drugs, providing differential data on their actions.
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