Naslov
Dependency of flavonoid binding in the IIA subdomain of human serum albumin with site and type of flavonoid substitution

Autori
Rimac, Hrvoje ; Weitner, Tin ; Bojić, Mirza ; Debeljak, Željko ; Medić-Šarić, Marica

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
8th World Congress on Polyphenols Application

Mjesto i datum
Lisabon, Portugal, 05.06.2014. - 06.06.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
flavonoids; HSA; binding; site substitution; type substitution

Sažetak
A large number of clinically important drugs with characterized by narrow therapeutic window bind in to the IIA subdomain of human serum albumin (HSA). In general, flavonoids also bind to the same subdomain, therefore it is plausible to hypothesize that flavonoid aglycones may be able to displace these drugs from HSA. This research investigates the impact of subsituent groups on flavonoid binding within IIA subdomain of HSA. The flavonoids in question belong to subgroups of flavones (apigenin, chrysin, chrysin dimethylether, diosmetine, flavone, 6-hydroxyflavone and 7-hydroxyflavone), flavonols (fisetin, galangin, quercetin, rhamnetin, tamarixetin, 6-hydroxyflavonol and 7-hydroxyflavonol), flavanones (flavanone, pinocembrin-7-methylether and sakuranetin) and isoflavones (formononetin, genistein and prunetin) (Figure 1.). Their binding constant to for IIA binding site was determined. All of the flavonoid solutions were prepared in 0.02 M potassium dihydrogen phosphate pH 7.4 : isopropanol = 1:1 (V/V) and the HSA solution in phosphate buffered saline. The concentration of HSA in the mixture was kept constant at 1.0 μM, while the concentration of flavonoids ranged from 0 μM to 100 μM. All of the measurements were conducted using fluorescence spectroscopy at λex = 280 nm and λem = 340 nm, by measuring the extinction of tryptophan produced fluorescence in the IIA binding site1, 2, 3. The results obtained showed that the sites, as well as the types of substitution (hydroxylation or methylation on positions 5, 7 and/or 4') had a great influence on the binding constant of studied flavonoids, up to 40-folds, with some sites and substituents influencing the constant more than the others.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA