期刊
NUCLEIC ACIDS RESEARCH
卷 49, 期 13, 页码 7256-7266出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab572
关键词
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资金
- BBSRC [BB/H019219/1]
- BBSRC [BB/H019219/1] Funding Source: UKRI
The introduction of the nucleobase 6-amino-5-nitropyridin-2-one (Z) enables stable and selective triplex formation of synthetic TFOs at neutral pH and above, overcoming the limitation of cytosine protonation at low pH. Furthermore, a universal strategy for enzymatic assembly of Z-containing TFOs using commercially available deoxyribonucleotide triphosphate has been demonstrated, aiming to improve the recognition properties of TFOs and reduce the cost and expertise associated with their chemical syntheses.
The sequence-specific recognition of duplex DNA by unmodified parallel triplex-forming oligonucleotides is restricted to low pH conditions due to a necessity for cytosine protonation in the third strand. This has severely restricted their use as gene-targeting agents, as well as for the detection and/or functionalisation of synthetic or genomic DNA. Here I report that the nucleobase 6-amino-5-nitropyridin-2-one (Z) finally overcomes this constraint by acting as an uncharged mimic of protonated cytosine. Synthetic TFOs containing the nucleobase enabled stable and selective triplex formation at oligopurine-oligopyrimidine sequences containing multiple isolated or contiguous GC base pairs at neutral pH and above. Moreover, I demonstrate a universal strategy for the enzymatic assembly of Z-containing TFOs using its commercially available deoxyribonucleotide triphosphate. These findings seek to improve not only the recognition properties of TFOs but also the cost and/or expertise associated with their chemical syntheses.
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