How Proximal Nucleobases Regulate the Catalytic Activity of G-Quadruplex/Hemin DNAzymes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F18%3A00501656" target="_blank" >RIV/68081707:_____/18:00501656 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1021/acscatal.8b03811" target="_blank" >http://dx.doi.org/10.1021/acscatal.8b03811</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acscatal.8b03811" target="_blank" >10.1021/acscatal.8b03811</a>

Jazyk výsledku

angličtina

Název v původním jazyce

How Proximal Nucleobases Regulate the Catalytic Activity of G-Quadruplex/Hemin DNAzymes

Popis výsledku v původním jazyce

G-quadruplexes (G4s) are versatile catalytic DNAs when combined with hemin. Despite the repertoire of catalytically competent G4/hemin complexes studied so far, little is known about the detailed catalytic mechanism of these biocatalysts. Herein, we have carried out an in-depth analysis of the hemin binding site within the G4/hemin catalysts, providing the porphyrinic cofactor with a controlled nucleotidic environment. We intensively assessed the position-dependent catalytic enhancement in model reactions and found that proximal nucleobases enhance the catalytic ability of the G4/hemin complexes. Our results allow for revisiting the mechanism of the G4/hemin-based catalysis, especially gaining insights into the rate-limiting step, demonstrating how both the G4 core and the proximal nucleotides dA and/or dC concomitantly activate the Compound 0> 0* prototropic cleavage of H2O2 to foster Compound 1 formation. These results provide mechanistic clues as to how the properties of G4-based catalysts can be improved to ultimately make them competitive with proteinaceous enzymes.

Název v anglickém jazyce

How Proximal Nucleobases Regulate the Catalytic Activity of G-Quadruplex/Hemin DNAzymes

Popis výsledku anglicky

G-quadruplexes (G4s) are versatile catalytic DNAs when combined with hemin. Despite the repertoire of catalytically competent G4/hemin complexes studied so far, little is known about the detailed catalytic mechanism of these biocatalysts. Herein, we have carried out an in-depth analysis of the hemin binding site within the G4/hemin catalysts, providing the porphyrinic cofactor with a controlled nucleotidic environment. We intensively assessed the position-dependent catalytic enhancement in model reactions and found that proximal nucleobases enhance the catalytic ability of the G4/hemin complexes. Our results allow for revisiting the mechanism of the G4/hemin-based catalysis, especially gaining insights into the rate-limiting step, demonstrating how both the G4 core and the proximal nucleotides dA and/or dC concomitantly activate the Compound 0> 0* prototropic cleavage of H2O2 to foster Compound 1 formation. These results provide mechanistic clues as to how the properties of G4-based catalysts can be improved to ultimately make them competitive with proteinaceous enzymes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACS Catalysis

ISSN

2155-5435

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

11352-11361

Kód UT WoS článku

000453491100037

EID výsledku v databázi Scopus

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