High Fidelity Enzyme-Free Primer Extension with an Ethynylpyridone Thymidine Analog.

C-nucleosides antivirals genetic copying nucleotides replication

Journal

Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783

Informations de publication

Date de publication:
17 Nov 2021
Historique:
received: 16 08 2021
pubmed: 25 9 2021
medline: 19 11 2021
entrez: 24 9 2021
Statut: ppublish

Résumé

High fidelity base pairing is important for the transmission of genetic information. Weak base pairs can lower fidelity, complicating sequencing, amplification and replication of DNA. Thymidine 5'-monophosphate (TMP) is the most weakly pairing nucleotide among the canonical deoxynucleotides, causing high errors rates in enzyme-free primer extension. Here we report the synthesis of an ethynylpyridone C-nucleoside analog of 3'-amino-2',3'-dideoxythymidine monophosphate and its incorporation in a growing strand by enzyme-free primer extension. The ethynylpyridone C-nucleotide accelerates extension more than five-fold, reduces misincorporation and readily displaces TMP in competition experiments. The results bode well for the use of the C-nucleoside as replacements for thymidine in practical applications.

Identifiants

pubmed: 34559417
doi: 10.1002/chem.202102996
pmc: PMC9293356
doi:

Substances chimiques

DNA Primers 0
Nucleotides 0
DNA 9007-49-2
Thymidine VC2W18DGKR

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

15918-15921

Subventions

Organisme : Deutsche Forschungsgemeinschaft
ID : project-ID 364653263 - TRR 235
Organisme : Volkswagen Foundation
ID : Az 92 768

Informations de copyright

© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.

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Auteurs

Jianyang Han (J)

Institut für Organische Chemie, Universität Stuttgart, 70569, Stuttgart, Germany.

Eric Kervio (E)

Institut für Organische Chemie, Universität Stuttgart, 70569, Stuttgart, Germany.

Clemens Richert (C)

Institut für Organische Chemie, Universität Stuttgart, 70569, Stuttgart, Germany.

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Classifications MeSH