Structural and Functional Impacts of Albumin Oxidation by Hypochlorite: Possible Changes in Drug Binding Characteristics upon Myeloperoxidase-Mediated Oxidation In Vivo
Journal Title: Journal of Reports in Pharmaceutical Sciences - Year 2012, Vol 1, Issue 2
Abstract
Interaction of drugs with serum albumin, the most abundant protein in plasma, has a great significance in pharmaceutical sciences. It can affect the biological activity, toxicity, and pharmacokinetics of drugs and design of dosages. Determination of the impact of chemical modifications of albumin and its structural changes upon interaction with drugs are very important when drugs bind with albumin to a significant degree. Hypochlorite is naturally produced by activated phagocytes in vivo at inflammatory conditions. In current study, the effects of hypochlorite-mediated oxidation on the albumin stability, surface hydrophobicity and its interaction with furosemide were investigated using intrinsic and extrinsic fluorescence techniques. Bovine serum albumin (BSA) was chemically modified with sodium hypochlorite under nondenaturing conditions. The Job’s plot indicated that the drug binds to the unmodified and modified BSAs with a 1:1 stoichiometry. Fluorescence quenching data showed that the albumin affinity for the drug as well as its surface hydrophobicity increases under the effect of protein oxidation. Measurement of conformational stability indicated that oxidized BSA is less stable compared to the unmodified protein. Thermodynamic analyses of the binding process showed that the major forces involved in the interaction of furosemide to the unmodified and oxidized BSA are same (hydrophobic). Increment of protein surface hydrophobicity (PSH) as well as the decrement of protein stability may reminiscent of higher protein structural flexibility upon oxidation which may affect the drug binding site.
Synthesis, Docking and Acetyl cholinesterase Inhibitory Evaluation of (E)-3-(4-(Diethyl amino) Phenyl)-1-Phenylprop-2-En-1-One Derivatives with Probable Anti-Alzheimer Effects
Alzheimer's disease (AD) as form of senile dementia is a cognitive and neurodegenerative disorder as well as behavioral and psychological problems in the geriatric people. The disease is characterized by memory deficit a...
RETRACTED:Molecular Docking And Molecular Dynamic Simulation Studies For Adenosine Deaminase Inhibitors As Therapeutic Targets
This article has been retracted at the request of the Editor-in-Chief and the Executive Manager. This paper has been withdrawn as a number of errors have subsequently been identified.
Chemical Composition of Volatile Oils from the Endocarp and Hulls of Persian Bay Laurel Fruit: A Fragrant Herb Used In Traditional Iranian Medicine
The hydro-distilled volatile oils, obtained from dried endocarp and hulls of Persian bay laurel (Laurus nobilis var. angustifolia) from Laueaceae family were analyzed by GC/MS. Thirteen and twelve compounds consisting 81...
Study of the Copolymer Structure Effect on Physicochemical Characteristics and In Vitro Stability of PLGA–PEG Nanoparticles Loaded 9-Nitrocamptothecin
9-nitrocamptothecin (9-NC) is a semisynthetic and a low soluble analogue of camptothecin alkaloids that target nuclear enzyme topoisomerase I. The unsTable lactone form of 9-NC in biological fluids requires for its cytot...
A Novel, Efficient, Fast and Inexpensive DNA Extraction Protocol from Whole Blood Applicable for Studying Drug-DNA Interaction
The DNA molecule has been known to be the cellular target for many cytotoxic anticancer agents for several decades. Understanding how drug molecules interact with DNA has become an active research area in the interface b...