Usefulness of difference spectroscopy in the study of the binding of uracil derivatives to human serum albumin.
Propylthiouracil is an antithyroid drug which is carried by the blood, thanks to its binding with human seroalbumin (HSA), and induces a structural alteration in HSA that changes the binding capability of other ligands. Then, with the aim of fixing the functional group in propylthiouracil involved in the interactions with HSA, the binding parameters for several uracil derivatives bound on HSA have been estimated. Interaction of propyluracil, thiouracil and propylthiouracil with HSA leads to the formation of complexes that show spectral shifts. These spectral shifts are a measure of the fraction of chromophoric groups, which is perturbed in the interaction with HSA, and thus can be used in the ligand binding estimate. The difference spectroscopy results correspond to the binding on a single centre in HSA. The difference spectra of propyluracils in seroalbumin coincide with those of propyluracils in a perturbant solvent (ethanol). On the other hand, propylthiouracil and propyluracil bind to seroalbumin on a larger scale than uracil and thiouracil. Thus, we can conclude that this binding is strengthened by hydrophobic interactions between the propyl group in propyluracils and apolar substituents on HSA.
Ochoa De Aspuru
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Departamento de Bioquímica y Biología Molecular, Universidad del País Vasco, Facultad de Farmacia, Vitoria, Spain.
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D006801:Humans; D011441:Propylthiouracil / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D014498:Uracil / Q000031:analogs & derivatives / Q000378:metabolism
D012709:Serum Albumin; D014498:Uracil; D011441:Propylthiouracil