Računalna analiza interakcija kvercetina i epigalokatehin-3-galata te njihovih metabolita sa serumskim albuminima

master's thesis

• Title (english): In silico analysis of interactions of quercetin and epigallocatechin-gallate (EGCG) as well as their metabolites with serum albumins
• Author: Sara Matić
• Mentor: Sanja Tomić (mentor)
• Mentor: Biljana Balen (mentor)
• Committee member: Biljana Balen (predsjednik povjerenstva)
• Committee member: Željka Vidaković-Cifrek (član povjerenstva)
• Committee member: Vesna Benković (član povjerenstva)
• Committee member: Ivana Ivančić Baće (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2016-06-29, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Polifenoli su aromatski sekundarni biljni metaboliti, za koje postoje brojni dokazi o povoljnom učinku na ljudsko zdravlje. Antioksidativne, antikancerogene i mnoge druge opažene aktivnosti polifenola ovise o njihovoj bioraspoloživosti. Budući da su polifenoli prisutni u plazmi metabolički modificirani, analizom glavnih komponenti uspoređen je utjecaj metilacije, sulfatacije i glukuronidacije te deprotonacije i dvostruke oksidacije na farmakokinetička svojstva kvercetina i katehina zelenog čaja. Ovi polifenoli se u plazmi vežu na serumski albumin, najzastupljeniji protein plazme, čija je najvažnija funkcija reverzibilno vezanje i transport velikog broja endogenih i egzogenih molekula. Utjecaj metaboličkih modifikacija na način i afinitet vezanja kvercetina i katehina u Sudlovljevo vezno mjesto 1 istražen je molekulskim uklapanjem u ljudski i goveđi serumski albumin pomoću programa AutoDock. Dobiveni rezultati su u skladu s dostupnim eksperimentalnim podacima iz literature. Sulfatacija se općenito pokazala najpovoljnijom modifikacijoma za vezanje ovih polifenola na oba albumina i mogla bi biti uzrokom kompeticije polifenola s lijekovima za vezanje na albumin u plazmi. Rezultati dobiveni za ljudski i goveđi albumin su međusobno značajno različiti što ukazuje da goveđi albumin nije povoljan analog humanom za istraživanje vezanja polifenola na serumski albumin. Također je deteljno ispitan utjecaj početnih struktura i parcijalnih atomskih naboja na rezultate molekulskog uklapanja AutoDockom.

Abstract (english)

Polyphenols are aromatic secondary plant metabolites, with numerous evidences for human health benefit. Antioxidative, anticancer and other activities of polyphenols depend on their free plasma concentration. Since polyphenols present in plasma are usually metabolically modified, the principle component analysis was used to study effects of methylation, sulfation and glucuronidation, as well as deprotonation and double oxidation, on pharmacokinetic properties of quercetin and green tea catechins. In plasma, these polyphenols bind to serum albumin, the most abundant plasma protein which reversibly binds various endogenous and exogenous compounds. In order to determine the effects of metabolic modifications of polyphenols on binding pose and affinity for Sudlow binding site 1, molecular docking was performed in human and bovine serum albumin using AutoDock. The results agree with available experimental data. Sulfation was shown to be the most favourable modification for binding of polyphenols to both albumins, and may be responsible for competition with drugs for binding to albumin. The results obtained for HSA and BSA were significantly different, pointing out that bovine albumin is not a suitable replacement for human analogue in affinity studies. Furthermore, effects of initial structures and partial atomic charges on the results of molecular docking with AutoDock have been studied.

• Keywords: polifenoli; serumski albumin; molekulsko uklapanje; analiza glavnih komponenti; farmakokinetička svojstva
• Keywords (english): polyphenols; serum albumin; molecular docking; principle component analysis; pharmacokinetic properties
• Language: croatian
• URN:NBN: urn:nbn:hr:217:409118
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-05-08 10:56:08