Properties of phosphoramide benzoazole oligonucleotides (PABAOs). I. Structure and hybridization efficiency of N-benzimidazole derivatives

Biochem Biophys Res Commun. 2024 Jan 22:693:149390. doi: 10.1016/j.bbrc.2023.149390. Epub 2023 Dec 14.

Abstract

In this work, we for the first time conducted a detailed study on the structure, dynamics, and hybridization properties of N-benzimidazole group-bearing phosphoramide benzoazole oligonucleotides (PABAOs) that we developed recently. By circular dichroism we established that the introduction of the modifications does not disrupt the B conformation of the DNA double helix. The formation of complexes is approximated by a two-state model. Complexes of PABAOs with native oligodeoxriboynucleotides form efficiently, and the introduction of such modifications reduces thermal stability of short duplexes (8-10 bp) by ∼5°С per modification. Using UV-spectroscopy analysis, a neutral charge of the phosphate residue modified by the N-benzimidazole moiety in the pH range of 3-9.5 was found. The results confirm possible usefulness of PABAOs for both basic research and biomedical applications.

Keywords: DNA hybridization; Determination of proton dissociation constant (pKa); N-benzimidazole; Nucleic acid derivatives; PABAO; Phosphoramide benzimidazole oligonucleotides; Structure; Thermodynamics.

MeSH terms

  • Circular Dichroism
  • DNA / chemistry
  • Nucleic Acid Conformation
  • Nucleic Acid Denaturation
  • Nucleic Acid Hybridization
  • Oligonucleotides* / chemistry
  • Phosphoramides*
  • Thermodynamics

Substances

  • Oligonucleotides
  • phosphoramide
  • Phosphoramides
  • DNA