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.

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  • EP ID EP340467
  • DOI -
  • Views 36
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How To Cite

(2012). Structural and Functional Impacts of Albumin Oxidation by Hypochlorite: Possible Changes in Drug Binding Characteristics upon Myeloperoxidase-Mediated Oxidation In Vivo. Journal of Reports in Pharmaceutical Sciences, 1(2), -. https://europub.co.uk./articles/-A-340467