GNA/aegPNA Chimera Loaded with RNA Binding Preference

Abstract

Pure and simple: A simple chimeric PNA (named chiPNA) was observed to selectively bind RNA in a 1:1 mixture of RNA and DNA with identical base sequences. This binding was assessed by chip‐based assay.

Base-pair Opening Dynamics of Nucleic Acids in Relation to Their Biological Function

“…PNAs are one of the most widely used synthetic DNA mimics where the four bases are attached to a N-(2-aminoethyl)glycine (aeg) backbone [103,104]. Chimeric PNA (chiPNA), in which a chiral glycerol nucleic acid-like γ 3 T monomer is incorporated into the aegPNA backbone, displays excellent RNA selectivity as well as antiparallel selectivity toward non-chimeric PNA [105]. Hydrogen exchange studies revealed that a aegPNA:DNA hybrid is a much more stable duplex (smaller K op ) and is less dynamic compared to the corresponding DNA duplex (longer τ 0 and τ open ) [38].…”

Base pair opening kinetics study of the aegPNA:DNA hydrid duplex containing a site-specific GNA-like chiral PNA monomer

“…Especially, the latter two may lead to poor specificity toward the target sequence, which give rise to undesirable effects both in biological and diagnostic applications. Recently, we have developed a structurally simple chiral PNA monomer with thymine base (named γ 3 T , Figure 1 B) and prepared a chimeric PNA (named chi PNA, Figure 1 C), in which γ 3 T monomers are incorporated into aeg PNA backbone ( 15 ). This chi PNA displays excellent RNA selectivity as well as antiparallel selectivity compared to aeg PNA although the melting temperatures of most chi PNA:DNA hybrids are slightly lower than the corresponding aeg PNA:DNA hybrids ( 15 ).…”

“…Recently, we have developed a structurally simple chiral PNA monomer with thymine base (named γ 3 T , Figure 1 B) and prepared a chimeric PNA (named chi PNA, Figure 1 C), in which γ 3 T monomers are incorporated into aeg PNA backbone ( 15 ). This chi PNA displays excellent RNA selectivity as well as antiparallel selectivity compared to aeg PNA although the melting temperatures of most chi PNA:DNA hybrids are slightly lower than the corresponding aeg PNA:DNA hybrids ( 15 ). Previous hydrogen exchange study using ammonia reported that the imino protons in the aeg PNA:DNA hybrid had similar base pair stabilities but very short base pair lifetimes compared to the corresponding DNA duplex ( 16 ).…”

γ3PNA: Peptide Analogue of Glycol Nucleic Acid

“…Previous study from our group has demonstrated that incorporation of a few γ 3 T into the aegPNA backbone (a chimeric PNA) can induce a preorganized helical propensity, by which the parent aegPNA was endowed with an improved binding preference to a target RNA. 6 This initial result has encouraged us to investigate the possibility of self-duplex formation of γ 3 PNA. Herein we report the synthetic methods for the preparation of monomers with other nucleobases (A, C, and G) as well as the thermal stability of γ 3 PNA duplex.…”

“…The common intermediate bromide 1 was easily prepared from (S)-epichlorohydrin (> 99%ee) in three steps (34% overall yield). 6,7 For the synthesis of γ 3 A, the bromide 1 was reacted with unprotected adenine base in the presence of sodium hydride in DMF for 48 hr at room temperature. After completion of the substitution reaction, the crude adduct was treated with excess amount of Boc anhydride, which unexpectedly resulted in bis-Boc protected product 3 in 61% overall yield.…”