TY - JOUR

T1 - Properties of phosphoramide benzoazole oligonucleotides (PABAOs). III. Structure and hybridization efficiency of N-benzothiazole derivatives

AU - Юшин, Иван Игоревич

AU - Голышев, Виктор Михайлович

AU - Барановская, Елизавета Евгеньевна

AU - Ломзов, Александр Анатольевич

N1 - This study was financially supported by the Russian Science Foundation (project no. 23-14-00358, https://rscf.ru/project/23-14-00358/).

PY - 2026/1/18

Y1 - 2026/1/18

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105025143962

U2 - 10.1016/j.bbrc.2025.153170

DO - 10.1016/j.bbrc.2025.153170

M3 - Article

C2 - 41422675

VL - 796

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

M1 - 153170

ER -