Lipid-linked nucleoside triphosphates for enzymatic synthesis of hydrophobic oligonucleotides with enhanced membrane anchoring efficiency

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00571288" target="_blank" >RIV/61388963:_____/23:00571288 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/23:10467090

Výsledek na webu

<a href="https://doi.org/10.1039/D2SC06718H" target="_blank" >https://doi.org/10.1039/D2SC06718H</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d2sc06718h" target="_blank" >10.1039/d2sc06718h</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Lipid-linked nucleoside triphosphates for enzymatic synthesis of hydrophobic oligonucleotides with enhanced membrane anchoring efficiency

Popis výsledku v původním jazyce

We designed and synthesized a series of 2'-deoxyribonucleoside triphosphates (dNTPs) bearing various lipid moieties. Fatty acid- and cholesterol-modified dNTPs proved to be substrates for KOD XL DNA polymerase in primer extension reactions. They were also mutually compatible for simultaneous multiple incorporations into the DNA strand. The methodology of enzymatic synthesis opened a pathway to diverse structurally unique lipid-ON probes containing one or more lipid units. We studied interactions of such probes with the plasma membranes of live cells. Employing a rational design, we found a series of lipid-ONs with enhanced membrane anchoring efficiency. The in-membrane stability of multiply modified ONs was superior to that of commonly studied ON analogues, in which a single cholesterol molecule is typically tethered to the thread end. Notably, some of the probes were detected at the cell surface even after 24 h upon removal of the probe solution. Such an effect was general to several studied cell lines.

Název v anglickém jazyce

Lipid-linked nucleoside triphosphates for enzymatic synthesis of hydrophobic oligonucleotides with enhanced membrane anchoring efficiency

Popis výsledku anglicky

We designed and synthesized a series of 2'-deoxyribonucleoside triphosphates (dNTPs) bearing various lipid moieties. Fatty acid- and cholesterol-modified dNTPs proved to be substrates for KOD XL DNA polymerase in primer extension reactions. They were also mutually compatible for simultaneous multiple incorporations into the DNA strand. The methodology of enzymatic synthesis opened a pathway to diverse structurally unique lipid-ON probes containing one or more lipid units. We studied interactions of such probes with the plasma membranes of live cells. Employing a rational design, we found a series of lipid-ONs with enhanced membrane anchoring efficiency. The in-membrane stability of multiply modified ONs was superior to that of commonly studied ON analogues, in which a single cholesterol molecule is typically tethered to the thread end. Notably, some of the probes were detected at the cell surface even after 24 h upon removal of the probe solution. Such an effect was general to several studied cell lines.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GX20-00885X" target="_blank" >GX20-00885X: Nové funkcionalizované (bio)polymery na bázi dekorace DNA malými molekulami</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Chemical Science

ISSN

2041-6520

e-ISSN

2041-6539

Svazek periodika

14

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

4059-4069

Kód UT WoS článku

000961816400001

EID výsledku v databázi Scopus

2-s2.0-85152106327