Sequence specificity of dimeric bisbenzimidazoles to AT-sequences of DNA of different nucleotide composition determined by footprinting
- 作者: 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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隶属关系:
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
- N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health
- 期: 卷 51, 编号 3 (2025)
- 页面: 408-417
- 栏目: ОБЗОРНАЯ СТАТЬЯ
- URL: https://rjonco.com/0132-3423/article/view/686910
- DOI: https://doi.org/10.31857/S0132342325030048
- EDN: https://elibrary.ru/KQCIMC
- ID: 686910
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详细
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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作者简介
D. 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
俄罗斯联邦, ul. Vavilova 32, Moscow, 119991; Kashirskoe shosse 24, Moscow, 115522
A. Arutuynyan
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: susovaolga@gmail.com
俄罗斯联邦, ul. Vavilova 32, Moscow, 119991
A. Beniaminov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: susovaolga@gmail.com
俄罗斯联邦, ul. Vavilova 32, Moscow, 119991
N. Smirnov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: susovaolga@gmail.com
俄罗斯联邦, ul. Vavilova 32, Moscow, 119991
D. Kaluzhny
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: susovaolga@gmail.com
俄罗斯联邦, ul. Vavilova 32, Moscow, 119991
A. Zhuze
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Email: susovaolga@gmail.com
俄罗斯联邦, ul. Vavilova 32, Moscow, 119991
O. Susova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health
编辑信件的主要联系方式.
Email: susovaolga@gmail.com
俄罗斯联邦, ul. Vavilova 32, Moscow, 119991; Kashirskoe shosse 24, Moscow, 115522
参考
- Wu K., Peng X., Chen M., Li Y., Tang G., Peng J., Peng Y., Cao X. // Chem. Biol. Drug. Des. 2022. V. 99. P. 736–757. https://doi.org/10.1111/cbdd.14022
- Tyagi Y.K., Jali G., Singh R. // Med. Chem. 2022. V. 22. P. 3280–3290. https://doi.org/10.2174/1871520622666220429134818
- Alniss H.Y., Al-Jubeh H.M., Msallam Y.A., Siddiqui R., Makhlouf Z., Ravi A., Hamdy R., Soliman S.S.M., Khan N.A. // Eur. J. Med. Chem. 2024. V. 271. P. 116440. https://doi.org/10.1016/j.ejmech.2024.116440
- Pan T., He X., Chen B., Chen H., Geng G., Luo H., Zhang H., Bai C. // Eur. J. Med. Chem. 2015. V. 5. P. 500–513. https://doi.org/10.1016/j.ejmech.2015.03.050
- Phan N.K., Huynh T.K., Nguyen H.P., Le Q.T., Nguyen T.C., Ngo K.K., Nguyen T.H., Ton K.A., Thai K.M., Hoang T.K. // ACS Omega. 2023. V. 28. P. 28733–28748. https://doi.org/10.1021/acsomega.3c03530
- Teng M.K., Usman N., Frederick C.A., Wang A.H. // Nucleic Acids Res. 1988. V. 25. P. 2671–2690. https://doi.org/10.1093/nar/16.6.2671
- Breusegem S.Y., Clegg R.M., Loontiens F.G. // J. Mol. Biol. 2002. V. 1. P. 1049–1061. https://doi.org/10.1006/jmbi.2001.5301
- Bazhulina N.P., Nikitin A.M., Rodin S.A., Surovaya A.N., Kravatsky Y.V., Pismensky V.F., Archipova V.S., Martin R., Gursky G.V. // J. Biomol. Struct. Dyn. 2009. V. 26. P. 701–718. https://doi.org/10.1080/07391102.2009.10507283
- Streltsov S.A., Gromyko A.V., Oleinikov V.A., Zhuze A.L. // J. Biomol. Struct. Dyn. 2006. V. 24. P. 285–302. https://doi.org/10.1080/07391102.2006.10507121
- Ivanov A.A., Salianov V.I., Strel’tsov S.A., Cherepanova N.A., Gromova E.S., Zhuze A.L. // Russ. J. Bioorg. Chem. 2011. V. 37. P. 530–541. https://doi.org/10.1134/s1068162011040054
- Ivanov A.A., Koval V.S., Susova O.Y., Salyanov V.I., Oleinikov V.A., Stomakhin A.A., Shalginskikh N.A., Kvasha M.A., Kirsanova O.V., Gromova E.S., Zhuze A.L. // Bioorg. Med. Chem. Lett. 2015. V. 1. P. 2634–2638. https://doi.org/10.1016/j.bmcl.2015.04.087
- Neidle S. // Nat. Prod. Rep. 2001. V. 18. P. 291–309. https://doi.org/10.1039/a705982e
- Susova O.Y., Karshieva S.S., Kostyukov A.A., Moiseeva N.I., Zaytseva E.A., Kalabina K.V., Zusinaite E., Gildemann K., Smirnov N.M., Arutyunyan A.F., Zhuze A.L. // Act. Nat. 2024. V. 16. P. 86–100. https://doi.org/10.32607/actanaturae.27327
- Naberezhnov D.S., Kirsanov K.I., Glazunov V.Y., Belitskiy G.A., Yakubovskaya M.G. // Russ. Fundam. Res. 2015. V. 2. P. 5599–5604.
- Caneva R., De Simoni A., Mayol L., Rossetti L., Savino M. // Biochim. Biophys. Acta. 1997. V. 7. P. 93–97. https://doi.org/10.1016/s0167-4781(97)00091-2
- Isagulieva A.K., Kaluzhny D.N., Beniaminov A.D., Soshnikova N.V., Shtil A.A. // Int. J. Mol. Sci. 2022. V. 23. P. 8871. https://doi.org/10.3390/ijms23168871
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