Drug binding properties of glycosylated human serum albumin as measured by fluorescence and circular dichroism.
Binding properties of Sudlow's site-specific drugs to glycosylated human serum albumin (G-HSA) were investigated using fluorescence and circular dichroism (CD). Dansylamide, phenylbutazone and warfarin were used as site I-specific drugs, and dansylproline, ibuprofen and flufenamic acid were used as site II-specific ones. Similar changes in the fluorescence intensity of dansylamide occurred in the presence of both G-HSA and intact human serum albumin (HSA), while the fluorescence enhancement of dansylproline caused by G-HSA was extremely weakened in comparison with that by HSA. These results suggest that the glycosylation of HSA inhibits the binding of the site II-specific drug, dansylproline, to HSA, while it does not influence the binding of the site I specific drug, dansylamide. The induced ellipticities of the complexes of ibuprofen, flufenamic acid and phenyl butazone with G-HSA were diminished in comparison with those with HSA. With the complexes of warfarin, the induced ellipticity was enhanced. These CD results suggest that the glycosylation of HSA induces microenvironmental changes in the binding sites for the above site-specific drugs which influence the drug binding ability of HSA.
Okabe
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Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
Hashizume
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N
D001665:Binding Sites; D002942:Circular Dichroism; D003619:Dansyl Compounds / Q000378:metabolism; D005439:Flufenamic Acid / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D017127:Glycation End Products, Advanced; D006801:Humans; D007052:Ibuprofen / Q000378:metabolism; D010653:Phenylbutazone / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives / Q000378:metabolism; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D014859:Warfarin / Q000378:metabolism; D000093423:Glycated Serum Albumin
D003619:Dansyl Compounds; D005456:Fluorescent Dyes; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; C086697:dansylproline; C001026:5-dimethylaminonaphthalene-1-sulfonamide; D014859:Warfarin; D005439:Flufenamic Acid; D011392:Proline; D010653:Phenylbutazone; D007052:Ibuprofen; D000093423:Glycated Serum Albumin