Skoči na glavni sadržaj

ADMET and DMPK, Vol. 2 No. 2, 2014.

Izvorni znanstveni članak

https://doi.org/10.5599/admet.2.2.28

Human Serum Albumin Binding of 2-[(Carboxymethyl)sulfanyl]-4-oxo-4-(4-tert-butylphenyl)butanoic Acid and its Mono-Me Ester

Ilija N. Cvijetić orcid id orcid.org/0000-0002-5568-6172 ; Innovation Center of the Faculty of Chemistry, University of Belgrade, Studentski Trg 16, 11000 Belgrade, Serbia
Dušan D. Petrović ; Faculty of Chemistry, University of Belgrade, Studentski Trg 16, 11000 Belgrade, Serbia
Tatjana Ž. Verbić orcid id orcid.org/0000-0002-6348-1644 ; Faculty of Chemistry, University of Belgrade, Studentski Trg 16, 11000 Belgrade, Serbia
Ivan O. Juranić orcid id orcid.org/0000-0003-1049-9725 ; Department of Chemistry-IChTM, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia
Branko J. Drakulić ; Department of Chemistry-IChTM, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia

Puni tekst: engleski pdf 2.443 Kb

str. 126-142

preuzimanja: 761

citiraj

Sažetak

Interactions of 2-[(carboxymethyl)sulfanyl]-4-oxo-4-(4-tert-butylphenyl)butanoic acid (compound 1) and its mono-Me ester (compound 2) with the human serum albumin (HSA) have been studied by fluorescence spectroscopy. Comp. 1 exerts antiproliferative activity toward human tumor cells and significant selectivity (tumor vs. healthy cells) in vitro. Competitive binding study with warfarin and ibuprofen as binding site probes, revealed that one molecule of comp. 1 selectively binds to HSA Sudlow site I (warfarin site) with moderate binding constant (Kb = (2.8 ± 0.5) x 104 M-1 at 37 ± 1 oC), while comp. 2 binds to Sudlow site II (Kb = (3.2 ± 0.9) x 104 M-1 at 37 ± 1 oC). Fluorescence quenching at different temperatures was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. Energy resonance transfer between HSA and comp. 1 was examined according to Förster’s non-radiative energy transfer theory. Distance of about 10 Å between ligand and Trp214 (HSA) was obtained. Docking studies confirmed HSA Sudlow site I as a preferable comp. 1 binding site, and Sudlow site II as comp. 2 binding site. Molecular dynamics simulations proved the stability of comp. 1/HSA complex.

Ključne riječi

Fluorescence spectroscopy; competitive binding; molecular dynamics; molecular docking

Hrčak ID:

125178

URI

https://hrcak.srce.hr/125178

Datum izdavanja:

18.7.2014.

Posjeta: 1.347 *