RESUMEN
The interaction between serum albumin (SA) and drugs has provided an interesting ground for understanding of drug effects, especially in drug distribution and drug-drug interaction on SA, in the case of multi-drug therapy. Determination of the impact of various factors on drug-protein interaction is especially important upon significant binding of drug to albumin. In the present study, the interaction of two drugs (furosemide and indomethacin) with native and modified albumins were investigated by using various spectroscopic methods. Fluorescence data indicated that 1:1 binding of drugs to bovine serum albumin (BSA) is associated with quenching of albumin intrinsic fluorescence. The Job's plot also confirmed that drug binds to BSA via mentioned stoichiometry. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between drug and albumin may change upon protein modification. The theoretical analyses also suggested some conformational changes of interacting side chains in subdomain IIA binding site (at the vicinity of W237), which were in good agreement with experimental data. Decrease of protein surface hydrophobicity (PSH) was also observed upon both albumin modification and drug binding.
Asunto(s)
Antiinflamatorios no Esteroideos/metabolismo , Diuréticos/metabolismo , Furosemida/metabolismo , Indometacina/metabolismo , Albúmina Sérica Bovina/metabolismo , Animales , Sitios de Unión , Bovinos , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Unión Proteica , Albúmina Sérica Bovina/química , Espectrometría de Fluorescencia , Análisis EspectralRESUMEN
It is well accepted that porphyrins related to heme, are effectively able to act as pharmaceutical. For instance, they were found to interfere with the aggregation of beta-amyloid peptide. In present study, the influence of heme concentration on the amyloid-type aggregation of ovalbumin was investigated. We provided experimental evidence of heme's prevention of ovalbumin aggregation in the heat-denaturation process using spectroscopic measurements. Different types of interactions were suggested to be involved in heme-ovalbumin amyloid communication. Since the consequence of heme-attenuated fibrillogenesis is yet to be identified, additional data on chaperoning role of heme may help us to manage amyloid aggregation processes.