Hydrophobic alkyl-linked base-modified pyrimidine and 7-deazapurine 2′-deoxyribonucleoside phosphoramidites: synthesis and application in solid-phase synthesis of modified and hypermodified oligonucleotides

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00643381" target="_blank" >RIV/61388963:_____/25:00643381 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/25:10509635

Výsledek na webu

<a href="https://doi.org/10.1039/D5RA06147D" target="_blank" >https://doi.org/10.1039/D5RA06147D</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d5ra06147d" target="_blank" >10.1039/d5ra06147d</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Hydrophobic alkyl-linked base-modified pyrimidine and 7-deazapurine 2′-deoxyribonucleoside phosphoramidites: synthesis and application in solid-phase synthesis of modified and hypermodified oligonucleotides

Popis výsledku v původním jazyce

A series of 2′-deoxyribonucleoside 3′-phosphoramidites bearing hydrophobic alkyl-linked modifications at nucleobases was synthesized, namely 5-phenylethyluracil, 5-pentylcytosine, 7-(indol-3-yl)ethyl-7-deazaadenine, and 7-isopentyl-7-deazaguanine derivatives. These nucleoside phosphoramidites were used for solid-phase synthesis of modified and hypermodified oligonucleotides containing up to fifteen modified nucleotides in a row. Their hybridization with complementary non-modified or modified oligonucleotides and thermal stability of the resulting DNA duplexes was studied using UV-vis denaturing experiments and CD spectroscopy. The results indicate that the partially modified hydrophobic DNA can still retain B-conformation, although with lower thermal stability. On the other hand, the hypermodified ONs containing all four modified nucleotides did not hybridize to duplexes likely due to formation of aggregates as indicated by dynamic light scattering measurement. This work expands the toolkit of chemically modified nucleotides for applications in functional nucleic acids or nucleic acid therapeutics, but also shows the scope and limitations of the use of hydrophobic nucleotides in hypermodified oligonucleotides and DNA.

Název v anglickém jazyce

Hydrophobic alkyl-linked base-modified pyrimidine and 7-deazapurine 2′-deoxyribonucleoside phosphoramidites: synthesis and application in solid-phase synthesis of modified and hypermodified oligonucleotides

Popis výsledku anglicky

A series of 2′-deoxyribonucleoside 3′-phosphoramidites bearing hydrophobic alkyl-linked modifications at nucleobases was synthesized, namely 5-phenylethyluracil, 5-pentylcytosine, 7-(indol-3-yl)ethyl-7-deazaadenine, and 7-isopentyl-7-deazaguanine derivatives. These nucleoside phosphoramidites were used for solid-phase synthesis of modified and hypermodified oligonucleotides containing up to fifteen modified nucleotides in a row. Their hybridization with complementary non-modified or modified oligonucleotides and thermal stability of the resulting DNA duplexes was studied using UV-vis denaturing experiments and CD spectroscopy. The results indicate that the partially modified hydrophobic DNA can still retain B-conformation, although with lower thermal stability. On the other hand, the hypermodified ONs containing all four modified nucleotides did not hybridize to duplexes likely due to formation of aggregates as indicated by dynamic light scattering measurement. This work expands the toolkit of chemically modified nucleotides for applications in functional nucleic acids or nucleic acid therapeutics, but also shows the scope and limitations of the use of hydrophobic nucleotides in hypermodified oligonucleotides and DNA.

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

2025

Kód důvěrnosti údajů

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

Název periodika

RSC Advances

ISSN

2046-2069

e-ISSN

2046-2069

Svazek periodika

15

Číslo periodika v rámci svazku

56

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

48556-48565

Kód UT WoS článku

001631965900001

EID výsledku v databázi Scopus

2-s2.0-105024751322