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Properties of phosphoramide benzoazole oligonucleotides (PABAOs). III. Structure and hybridization efficiency of
Ivan I Yushin1, Victor M Golyshev1, Elizaveta E Baranovskaya2
1Laboratory of Structural Biology, Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, 630090, Russia; Novosibirsk State University, Novosibirsk, 630090, Russia.
Abstract:
This study is focused on the investigation of structural, optical, and thermodynamic properties of phosphoramide benzoazole oligonucleotides (PABAOs) containing N-benzothiazole modifications (PABAO(S)). Using a combination of spectroscopic techniques, thermodynamic analysis, and molecular dynamics (MD) simulations, we characterized the acid-base behavior, hybridization efficiency, and conformational stability of PABAO(S) in comparison with previously reported N-benzimidazole and N-benzoxazole analogues. The pKa of the N-benzothiazole phosphoramidate moiety was determined to be 8.36, indicating its predominant protonation state at neutral pH value. UV-Vis and circular dichroism spectra did not reveal any significant changes in the geometry of the B-form duplex following the introduction of the modification. Thermal denaturation studies showed a reduction in melting temperature relative to native DNA, with an average decrease of ∼5 °C per modification under both standard (1 M NaCl) and near-physiological buffer conditions. Molecular dynamics simulations confirmed the structural integrity of modified duplexes and highlighted the influence of stereochemistry and protonation state on local conformation and hydrogen-bonding patterns. Overall, this work provides a systematic framework for understanding how azole ring substitutions modulate the physicochemical and hybridization properties of PABAOs, supporting their rational design as functional nucleic acid derivatives.
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