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.2022 May 26;20(20):4115-4122.
doi: 10.1039/d2ob00266c.

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

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

Keiji Murayama et al. Org Biomol Chem..

Abstract

We have synthesized acyclicallo-threoninol nucleic acids (allo-aTNAs), artificial xeno-nucleic acids (XNAs) that are diastereomers of acyclic threoninol nucleic acids (aTNAs), and have investigated their supramolecular properties. Theallo-aTNAs formed homo-duplexes in an antiparallel manner but with lower thermal stability than DNA, whereasaTNAs formed extremely stable homo-duplexes. Theallo-aTNAs formed duplexes with complementaryaTNAs and serinol nucleic acid (SNA). The affinities of L-allo-aTNA were the highest for L-aTNA and the lowest for D-aTNA, with SNA being intermediate. The affinities of D-allo-aTNA were the reverse. Circular dichroism measurements revealed that L- and D-allo-aTNAs had weak right-handed and left-handed helicities, respectively. The weak helicity ofallo-aTNAs likely explains the poor chiral discrimination of these XNAs, which is in contrast toaTNAs that have strong helical orthogonality. Energy-minimized structures of L-allo-aTNA/RNA and L-allo-aTNA/L-allo-aTNA indicated that the methyl group on theallo-aTNA strand is unfavourable for duplex formation. In contrast, the methyl group on L-aTNA likely stabilizes the duplex structurevia hydrophobic effects and van der Waals interactions. Thus, the configuration of the methyl group on the XNA scaffold had an unexpectedly large impact on the hybridization ability and structure.

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