Reactive OFF-ON type alkylating agents for higher-ordered structures of nucleic acids.
Alkylating Agents
/ chemical synthesis
Alkylation
Base Pairing
DNA
/ chemistry
DNA, Single-Stranded
/ chemistry
G-Quadruplexes
/ drug effects
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Nucleic Acid Conformation
/ drug effects
Purines
/ chemistry
Spectrometry, Mass, Electrospray Ionization
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Structure-Activity Relationship
Triazines
/ chemistry
Vinyl Compounds
/ chemistry
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
26 07 2019
26 07 2019
Historique:
accepted:
30
05
2019
revised:
15
05
2019
received:
08
01
2019
pubmed:
13
6
2019
medline:
7
1
2020
entrez:
13
6
2019
Statut:
ppublish
Résumé
Higher-ordered structure motifs of nucleic acids, such as the G-quadruplex (G-4), mismatched and bulge structures, are significant research targets because these structures are involved in genetic control and diseases. Selective alkylation of these higher-order structures is challenging due to the chemical instability of the alkylating agent and side-reactions with the single- or double-strand DNA and RNA. We now report the reactive OFF-ON type alkylating agents, vinyl-quinazolinone (VQ) precursors with a sulfoxide, thiophenyl or thiomethyl group for the OFF-ON control of the vinyl reactivity. The stable VQ precursors conjugated with aminoacridine, which bind to the G-4 DNA, selectively reacted with a T base on the G-4 DNA in contrast to the single- and double-strand DNA. Additionally, the VQ precursor reacted with the T or U base in the AP-site, G-4 RNA and T-T mismatch structures. These VQ precursors would be a new candidate for the T or U specific alkylation in the higher-ordered structures of nucleic acids.
Identifiants
pubmed: 31188442
pii: 5514191
doi: 10.1093/nar/gkz512
pmc: PMC6649768
doi:
Substances chimiques
2-amino-6-vinylpurine
0
2-vinyl-4,6-diamino-1,3,5-triazine
0
Alkylating Agents
0
DNA, Single-Stranded
0
Purines
0
Triazines
0
Vinyl Compounds
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6578-6589Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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