Sequence specificity of dimeric bisbenzimidazoles to AT-sequences of DNA of different nucleotide composition determined by footprinting
- Authors: Naberezhnov D.S.1,2, Arutuynyan A.F.1, Beniaminov A.D.1, Smirnov N.M.1, Kaluzhny D.N.1, Zhuze A.L.1, Susova O.Y.1,2
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Affiliations:
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
- N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health
- Issue: Vol 51, No 3 (2025)
- Pages: 408-417
- Section: ОБЗОРНАЯ СТАТЬЯ
- URL: https://ruspoj.com/0132-3423/article/view/686910
- DOI: https://doi.org/10.31857/S0132342325030048
- EDN: https://elibrary.ru/KQCIMC
- ID: 686910
Cite item
Abstract
The study aimed to investigate the site-specificity of binding to DNA of three series of minor groove ligands – dimeric bisbenzimidazoles DB2(n), DB2P(n), and DB2Py(n) – using DNAase I footprinting. The compounds consist of two bisbenzimidazole units linked by oligomethylene linkers of varying lengths (n), with structural modifications to enhance DNA-binding properties. The binding specificity of the compounds was determined using DNAase I footprinting. The DB2(n) and DB2P(n) series are analogs of Hoechst 33342, modified by removing hydrophobic ethoxyphenol cores and introducing hydrophilic aminomethylene groups. The DB2Py(n) series incorporates a pyrrolcarboxamide group, a structural unit of the AT-specific antibiotic netropsin. The interaction of these compounds with DNA sequences was analyzed to identify their binding preferences. All studied compounds demonstrated specificity for AT-rich DNA sequences. The DB2P(n) and DB2(n) series exhibited increased affinity for (AATT)3 and TTTT sequences. The DB2Py(n) series showed high specificity to AT-rich regions, with a preference for the TTTT motif. None of the compounds interacted with sequences containing fewer than four AT base pairs. These findings highlight the influence of structural modifications on DNA-binding specificity and affinity. The study revealed that dimeric bisbenzimidazoles DB2(n), DB2P(n), and DB2Py(n) exhibit distinct binding preferences for AT-rich DNA sequences, with DB2Py(n) showing a pronounced affinity for the TTTT motif. The results demonstrate the potential of these compounds as tools for targeting specific DNA sequences, with implications for molecular biology and drug design.
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About the authors
D. S. Naberezhnov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health
Email: susovaolga@gmail.com
Russian Federation, ul. Vavilova 32, Moscow, 119991; Kashirskoe shosse 24, Moscow, 115522
A. F. Arutuynyan
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: susovaolga@gmail.com
Russian Federation, ul. Vavilova 32, Moscow, 119991
A. D. Beniaminov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: susovaolga@gmail.com
Russian Federation, ul. Vavilova 32, Moscow, 119991
N. M. Smirnov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: susovaolga@gmail.com
Russian Federation, ul. Vavilova 32, Moscow, 119991
D. N. Kaluzhny
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: susovaolga@gmail.com
Russian Federation, ul. Vavilova 32, Moscow, 119991
A. L. Zhuze
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: susovaolga@gmail.com
Russian Federation, ul. Vavilova 32, Moscow, 119991
O. Y. Susova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health
Author for correspondence.
Email: susovaolga@gmail.com
Russian Federation, ul. Vavilova 32, Moscow, 119991; Kashirskoe shosse 24, Moscow, 115522
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