5-Substituted Pyrimidine and 7-Substituted 7-Deazapurine dNTPs as Substrates for DNA Polymerases in Competitive Primer Extension in the Presence of Natural dNTPs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00469259" target="_blank" >RIV/61388963:_____/16:00469259 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/16:10330187

Výsledek na webu

<a href="http://pubs.acs.org/doi/full/10.1021/acschembio.6b00714" target="_blank" >http://pubs.acs.org/doi/full/10.1021/acschembio.6b00714</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acschembio.6b00714" target="_blank" >10.1021/acschembio.6b00714</a>

Jazyk výsledku

angličtina

Název v původním jazyce

5-Substituted Pyrimidine and 7-Substituted 7-Deazapurine dNTPs as Substrates for DNA Polymerases in Competitive Primer Extension in the Presence of Natural dNTPs

Popis výsledku v původním jazyce

A complete series of 5-substituted uracil or cytosine, as well as 7-substituted 7-deazaadenine and 7-deazaguanine 2'-deoxyribonucleoside triphosphates (dNTPs) bearing substituents of increasing bulkiness (H, Me, vinyl, ethynyl, and phenyl) were systematically studied in competitive primer extension in the presence of their natural counterparts (nonmodified dNTPs), and their kinetic data were determined. The results show that modified dNTPs bearing, pi-electron containing substituents (vinyl, ethynyl, Ph) are typically excellent substrates for DNA polymerases comparable to or better than natural dNTPs. The kinetic studies revealed that these modified dNTPs have higher affinity to the active site of the enzyme primer template complex, and the calculations (semiempirical quantum mechanical scoring function) suggest that it is due to the cation-pi interaction of the modified dNTP with Arg629 in the active site of Bst DNA polymerase.

Název v anglickém jazyce

5-Substituted Pyrimidine and 7-Substituted 7-Deazapurine dNTPs as Substrates for DNA Polymerases in Competitive Primer Extension in the Presence of Natural dNTPs

Popis výsledku anglicky

A complete series of 5-substituted uracil or cytosine, as well as 7-substituted 7-deazaadenine and 7-deazaguanine 2'-deoxyribonucleoside triphosphates (dNTPs) bearing substituents of increasing bulkiness (H, Me, vinyl, ethynyl, and phenyl) were systematically studied in competitive primer extension in the presence of their natural counterparts (nonmodified dNTPs), and their kinetic data were determined. The results show that modified dNTPs bearing, pi-electron containing substituents (vinyl, ethynyl, Ph) are typically excellent substrates for DNA polymerases comparable to or better than natural dNTPs. The kinetic studies revealed that these modified dNTPs have higher affinity to the active site of the enzyme primer template complex, and the calculations (semiempirical quantum mechanical scoring function) suggest that it is due to the cation-pi interaction of the modified dNTP with Arg629 in the active site of Bst DNA polymerase.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA14-04289S" target="_blank" >GA14-04289S: Modifikace a bioorthogonální reakce ve velkém žlábku DNA pro regulaci vazby proteinů a genové exprese</a><br>

Návaznosti

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

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

ACS Chemical Biology

ISSN

1554-8929

e-ISSN

1554-8937

Svazek periodika

11

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

3165-3171

Kód UT WoS článku

000388430100025

EID výsledku v databázi Scopus

2-s2.0-84996721494