Microenvironmental Analysis of Drug Binding Sites on Human Serum Albumin and alpha_1-Acid Glycoprotein

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The present study was undertaken in a view to clarify the characteristics of the drug binding sites on human serum albumin(HSA)and alpha_1-acid glycoprotein(AGP)using different fluorescent probes whose binding are site specific to HSA and AGP. Results obtained are as follows.(1)Hydrophobic forces were the driving forces for the binding of drugs to both HSA and AGP as evidenced from the obtained correlation of binding affinities with partition coefficients, the thermodynamic analysis and the spectral analysis. Further, sialic acid was found to impart some role in the binding of drugs to AGP.(2)From the displacement data using the fluorescent probes it seems that there are three drug binding sites on HSA andone widened flexible drug binding site on AGP, respectively. Although the presence of three different binding sites on HSA is evidenced, it is rather reasonable to consider that these sites are not completely separated but significantly overlapped and influenced by each other.(3)The hydrophobicity of the drug binding sites on HSA were in the order of site II>site I>siteIII. For AGP, one drug binding area was evidenced, however, the hydrophobicity of the acidic drug binding site was found to be greater than that of basic drug binding site. Moreover, the binding sizes of the sites on HSA or AGP were found to be different. In addition, the microviscosity analysis, a newly developed method, also suggested that the flexibility of the site I was the smallest among all the drug binding sites on HSA and the acidic drug binding site was more flexible as compared with the basic drug binding site.