The 2-Aminopyridine Nucleobase Improves Triple-Helical Recognition of RNA and DNA When Used Instead of Pseudoisocytosine in Peptide Nucleic Acids

被引:20
作者
Ryan, Christopher A. [1 ]
Brodyagin, Nikita [1 ]
Lok, Justin [1 ]
Rozners, Eriks [1 ]
机构
[1] SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
SEQUENCE-SELECTIVE RECOGNITION; DOUBLE-STRANDED DNA; FORMING OLIGONUCLEOTIDES; PNA; 2-O-METHYLPSEUDOISOCYTIDINE; NUCLEOSIDES; ANALOGS; DUPLEX; PH;
D O I
10.1021/acs.biochem.1c00275
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pseudoisocytosine (J), a neutral analogue of protonated cytosine, is currently the gold standard modified nucleobase in peptide nucleic acids (PNAs) for the formation of J.G-C triplets that are stable at physiological pH. This study shows that triple-helical recognition of RNA and DNA is significantly improved by using 2-aminopyridine (M) instead of J. The positively charged M forms 3-fold stronger M+-G-C triplets than J with uncompromised sequence selectivity. Replacement of six Js with Ms in a PNA 9-mer increased its binding affinity by similar to 2 orders of magnitude. M-modified PNAs prefer binding double-stranded RNA over DNA and disfavor off-target binding to single-stranded nucleic acids. Taken together, the results show that M is a promising modified nucleobase that significantly improves triplex-forming PNAs and may provide breakthrough developments for therapeutic and biotechnology applications.
引用
收藏
页码:1919 / 1925
页数:7
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