2-Guanidyl pyridine PNA nucleobase for triple-helical Hoogsteen recognition of cytosine in double-stranded RNA

Abstract

In triplex-forming peptide nucleic acid, a novel 2-guanidyl pyridine nucleobase (V) enables recognition of up to two cytosine interruptions in polypurine tracts of dsRNA by engaging the entire Hoogsteen face of C–G base pair.

Nucleobase and Linker Modification for Triple‐Helical Recognition of Pyrimidines in RNA Using Peptide Nucleic Acids

“…This binding mode was also observed with the V base in our recent study. [19] However, in contrast to V, we did not observe additional hydrogen bonds stabilizing the extended linker. The thiazole ring had minimal π-π stacking interactions.…”

“…PNA monomers X 1 -X 10 were incorporated in PNA1 (Figure 2) using our previously reported methods. [14,[18][19] The stability and sequence specificity of triplexes formed between PNAs modified with various heterocycles (X N in PNA1, Figure 2) and model hairpins HRP1-HRP4 was measured using UV thermal melting at 300 nm as previously reported. [14,[18][19] We started our study with simple amino-substituted "abasic" modifications X 1 and X 2 derived from glycine and β-alanine, respectively.…”

“…[14,[18][19] The stability and sequence specificity of triplexes formed between PNAs modified with various heterocycles (X N in PNA1, Figure 2) and model hairpins HRP1-HRP4 was measured using UV thermal melting at 300 nm as previously reported. [14,[18][19] We started our study with simple amino-substituted "abasic" modifications X 1 and X 2 derived from glycine and β-alanine, respectively. Not surprisingly, these modifications showed similar affinity as P 10 in our previous study [18] and displayed little, if any, sequence selectivity (Table 1).…”

“…[18] Most recently, we reported that 2-guanidylpyridine (V in Figure 1) nucleobase formed strong PNA-dsRNA triplexes having a single V * C-G interruption. [19] Chen and co-workers have used guanidinylethyl-5-methylcytosine with similar success. [20] Despite these promising results, recognition of two or more pyrimidines was problematic in most studies (for a notable exception, see Kim et al [16a] ) and triple-helical binding to any sequence of dsRNA or dsDNA is still an unsolved problem in molecular recognition of nucleic acids.…”

Supernatural: Artificial Nucleobases and Backbones to Program Hybridization-Based Assemblies and Circuits

“…In parallel, efforts to extend the hydrogen-bond network beyond classical Hoogsteen interactions have yielded artificial nucleobases that enhance triplex formation to pyrimidines. Nucleobases such as D3 , , Q , , V , and S − and aminopyridinyl-pseudodeoxycytosine were designed to target pyrimidines but also extend in order to interact with the purine in G - C and A -T pairs (Figure D, pink). Such designs hold great potential to improve the stability and universal recognition of triplexes.…”