Unexpectedly Stable Artificial Duplex from Flexible Acyclic Threoninol

Abstract

A new foldamer, acyclic threoninol nucleic acid (aTNA), has been synthesized by tethering each of the genetic nucleobases A, G, C, and T to d-threoninol molecules, which were then incorporated as building blocks into a scaffold bearing phosphodiester linkages. We found that with its fully complementary strand in an antiparallel fashion, the aTNA oligomer forms an exceptionally stable duplex that is far more stable than corresponding DNA or RNA duplexes, even though single-stranded aTNA is rather flexible and thus does not take a preorganized structure.

Highly Stable Duplex Formation by Artificial Nucleic Acids Acyclic Threoninol Nucleic Acid (aTNA) and Serinol Nucleic Acid (SNA) with Acyclic Scaffolds

“…Hybridization of ­ a TNA and SNA with other types of oligonucleotides : We next investigated the abilities of a TNA and SNA to pair with other types of oligonucleotides (Table S1 in the Supporting Information, Figure 4). As we reported previously, a TNA does not form a duplex with complementary DNA or RNA (Figure S3a in the Supporting Information) 17. The SNA/DNA combinations ( S8 a/D8 b and D8 a/S8 b ) showed sigmoidal melting curves ( T m values of 23.5 and 21.2 °C, respectively).…”

“…Keywords: DNA · helical structures · melting temperature · nucleic acids · thermodynamics spired by acyclic GNA, we have synthesized two novel artificial nucleic acids: acyclic threoninol nucleic acid (aTNA) and serinol nucleic acid (SNA), [17,18] with acyclic d-threoninol and l-serinol as backbones, respectively ( Figure 1). These nucleic acids should be more flexible than GNA due to the additional methylene chain.…”

“…SNA forms stable heteroduplexes with both DNA and RNA; aTNA does not crosshybridize with either DNA or RNA. [17,18] Peptide nucleic acids (PNAs) are another artificial nucleic acid with an acyclic scaffold. [19,20] The extremely high stabilities of PNA/PNA, PNA/DNA, and PNA/RNA duplexes are generally ascribed to the absence of electrostatic repulsion between the two strands due to the lack of negative charge on PNA.…”

DNA functionalization by dynamic chemistry

“…As presented in Scheme 1 phosphoramidite 4 was obtained according to the procedures previously described in literature [14,23]. …”

“…Synthesis of the phosphoramidite building block 4 [23]. DMTr: dimethoxytrityl group, Fmoc: 9-fluorenylmethylcarbonyl, DMAP: 4-dimethylaminopyridine, DIEA: N,N -diisopropylethylamine.…”