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

Abstract

New phosphate-modified nucleic acid derivatives are of great significance in basic research and biomedical applications. We have recently developed a new class of phosphoramide benzoazole oligonucleotides (PABAOs). In this work, th properties of N-benzoxazole oligodeoxyribonucleotides have been thoroughly examined. We have demonstrated the convenient automated solid-phase synthesis of oligomers with a different number of modifications (up to six) at various positions. Optical properties, thermal stability, structure, and dynamics of PABAO/DNA complexes have been investigated. The N-benzoxazole-modified phosphate group is uncharged at neutral pH and has a pKa value of 8.52. Structural analysis performed by the CD spectroscopy and MD simulation indicate B-form of PABAO/DNA duplexes. The thermal stability of PABAO/DNA complexes bearing N-benzoxazole is reduced by 2.5-6.2° per modification compared to native duplexes at standard and near physiological buffer conditions. The performed study underlines a great potential of phosphoramide benzoazole oligonucleotides for basic research, applied sciences, and biotechnology.