Sequence-Selective Recognition of DNA by Strand Displacement with a Thymine-Substituted Polyamide

TLDR

A polyamide nucleic acid was engineered by replacing the DNA backbone with an achiral polyamide backbone and synthesized as thymine‑linked aminoethylglycyl oligomers, enabling strand displacement through highly stable PNA‑DNA hybrids. The resulting polyamide oligomers specifically recognize complementary DNA sequences and displace strands, demonstrating that a DNA backbone can be replaced while preserving base‑specific hybridization.

Abstract

A polyamide nucleic acid (PNA) was designed by detaching the deoxyribose phosphate backbone of DNA in a computer model and replacing it with an achiral polyamide backbone. On the basis of this model, oligomers consisting of thymine-linked aminoethylglycyl units were prepared. These oligomers recognize their complementary target in double-stranded DNA by strand displacement. The displacement is made possible by the extraordinarily high stability of the PNA-DNA hybrids. The results show that the backbone of DNA can be replaced by a polyamide, with the resulting oligomer retaining base-specific hybridization.