Nonenzymatic polymerase-like template-directed synthesis of acyclic l-threoninol nucleic acid

Abstract

Evolution of xeno nucleic acid (XNA) world essentially requires template-directed synthesis of XNA polymers. In this study, we demonstrate template-directed synthesis of an acyclic XNA, acyclicl-threoninol nucleic acid (l-aTNA), via chemical ligation mediated by N-cyanoimidazole. The ligation of an l-aTNA fragment on an l-aTNA template is significantly faster and occurs in considerably higher yield than DNA ligation. Both l-aTNA ligation on a DNA template and DNA ligation on an l-aTNA template are also observed. High efficiency ligation of trimer l-aTNA fragments to a template-bound primer is achieved. Furthermore, a pseudo primer extension reaction is demonstrated using a pool of random l-aTNA trimers as substrates. To the best of our knowledge, this is the first example of polymerase-like primer extension of XNA with all four nucleobases, generating phosphodiester bonding without any special modification. This technique paves the way for a genetic system of the l-aTNA world.

Xeno nucleic acids (XNAs) having non-ribose scaffolds with unique supramolecular properties

“…Our group investigated the chemical ligation of L-aTNA in the presence of various templates using cyanoimidazole (CNIm) and Mn 2+ as an activator. 81 Interestingly, the rate of ligation of L-aTNA on a L-aTNA template was about 50-fold faster than that of DNA under the same conditions. Note that L-aTNA did not have to replace the hydroxyl group with a more nucleophilic amino group.…”

“…14). 81 Due to the extremely high ligation efficiency, it was not necessary to use three complementary trimers. In the reaction in the presence of a random trimer pool synthesized from l - a TNA phosphoramidites of four nucleobases, more than 75% of the primer was elongated to the 17-mer full-length product at 4 °C after a 24-hour incubation (Fig.…”

Design and Hybridization Properties of Acyclic Xeno Nucleic Acid Oligomers

“…The flexible acyclic scaffold of a TNA apparently allow formation of these non‐canonical structures. Recently, we established nonenzymatic primer extension reaction of L‐ a TNA using a pool of random trimer fragments as substrates, indicating that L‐ a TNA could have been a precursor of RNA [54] …”

Methyl group configuration on acyclic threoninol nucleic acids (aTNAs) impacts supramolecular properties

“…[7][8][9][10] Recently, XNAs have also been investigated as a synthetic genetic material and potential genetic material under prebiotic conditions. 3,[11][12][13][14][15][16] The hybridization abilities and duplex structures of XNA oligomers depend on the chemical structure of the scaffold. XNAs composed of cyclic backbones, such as locked or bridged nucleic acids, 17,18 stabilize the duplex by entropic effects due to pre-organization of the rigid main chain.…”