A Simple γ-Backbone Modification Preorganizes Peptide Nucleic Acid into a Helical Structure

TLDR

Peptide nucleic acid (PNA) is a synthetic analogue of DNA and RNA that lacks a well‑defined helical conformation in solution, unlike its natural counterparts. The study aims to demonstrate that a simple γ‑position backbone modification of the N‑(2‑aminoethyl) glycine unit can preorganize PNA into a helical structure. Spectroscopic analysis revealed that this helical induction proceeds from the C‑ to N‑terminal direction, is sterically driven, and suggests new avenues for designing nucleic acid mimics and materials with efficient electronic coupling.

Abstract

Peptide nucleic acid (PNA) is a synthetic analogue of DNA and RNA, developed more than a decade ago in which the naturally occurring sugar phosphate backbone has been replaced by the N-(2-aminoethyl) glycine units. Unlike DNA or RNA in the unhybridized state (single strand) which can adopt a helical structure through base-stacking, although highly flexible, PNA does not have a well-defined conformational folding in solution. Herein, we show that a simple backbone modification at the γ-position of the N-(2-aminoethyl) glycine unit can transform a randomly folded PNA into a helical structure. Spectroscopic studies showed that helical induction occurs in the C- to N-terminal direction and is sterically driven. This finding has important implication not only on the future design of nucleic acid mimics but also on the design of novel materials, where molecular organization and efficient electronic coupling are desired.