Synthesis of a bisbenzoxazole analogue of Hoechst 33258 as a Potential GC-Selective Dna Ligand

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Using a computer modelling approach we proposed the structure of a potential GC-specific DNA ligand, which could form a complex with DNA in the minor groove similar to that formed by Hoechst 33258 at DNA AT-enriched sites. According to this model MBoz2A, a bisbenzoxazole ligand, was synthesized. The results of spectrophotometric methods supported the complex formation of the compound under study with DNA differed in the nucleotide composition.

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作者简介

A. Arutuynyan

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: zhuze@eimb.ru
俄罗斯联邦, Moscow, 119991

M. Aksenova

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: zhuze@eimb.ru
俄罗斯联邦, Moscow, 119991

A. Kostyukov

Emanuel Institute of Biochemical Physics, Russian Academy of Science

Email: zhuze@eimb.ru
俄罗斯联邦, Moscow, 119334

A. Stomakhin

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: zhuze@eimb.ru
俄罗斯联邦, Moscow, 119991

D. Kaluzhny

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: zhuze@eimb.ru
俄罗斯联邦, Moscow, 119991

A. Zhuze

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

编辑信件的主要联系方式.
Email: zhuze@eimb.ru
俄罗斯联邦, Moscow, 119991

参考

  1. Geierstanger B.H., Wemmer D.E. (1995) Complexes of the minor groove of DNA. Annu. Rev. Biophys. Biomol. Structure. 24, 463–493.
  2. Krey A.K., Hahn F.E. (1970) Studies on the complex of distamycin A with calf thymus DNA. FEBS Lett. 10, 175–178.
  3. Harshman K.D., Dervan P.B. (1985) Molecular recognition of B-DNA by Hoechst 33258. Nucl. Acids Res. 13, 4825–48354.
  4. Dervan P.B. (2001) Molecular recognition of DNA by small molecules. Bioorg. Med. Chem. 9, 2215–2235.
  5. Dervan P.B., Buerli R.W. (1999) Sequence-specific DNA recognition by polyamides. Curr. Opin. Chem. Biol. 3, 688–693.
  6. Wemmer D.E., Dervan P.B. (1997) Targeting the minor groove of DNA. Curr. Opin. Struct. Biol. 7, 355–361.
  7. Dervan P.B., Doss R.M., Marques M.A. (2005) Programmable DNA binding oligomers for control of transcription. Curr. Med. Chem. Anti-Cancer Agents. 5, 373–387.
  8. Guo P., Paul A., Kumar A., Farahat A.A., Kumar D., Wang S., Boykin D.W., Wilson D.W. (2016) The thiophene “sigma-hole” as a concept for preorganized, specific recognition of G.C base pairs in the DNA minor groove. Chem. Eur. J. 22, 15404–15412.
  9. Guo P., Farahat A.A., Paul A., Hanka N.K., Boykin D.V., Wilson W.D. (2018) Compound shape effects in minor groove binding affinity and specificity for mixed sequence DNA. J. Am. Chem. Soc. 140, 14761–14769.
  10. Wilson W.D., Paul A. (2023) Compound shape and substituent effects in DNA minor groove interactions. In: Handbook of Chemical Biology of Nucleic Acids. Еd. Sugimoto N. Singapore: Springer, pp. 1‒39.
  11. Paul A., Nanjunda R., Wilson W.D. (2023) Binding to the DNA minor groove by heterocyclic dications from AT specific to GC recognition compounds. Curr. Protocols. 3(4), e729.
  12. O’Boyle N.M., Banck M., Craig A.J., Morley C., Vandermeersch T., Hutchison G.R. (2011) Open Babel: an open chemical toolbox. J. Cheminformatics. 3, 1–14.
  13. Korb O., Stützle T., Exner T.E. (2007) An ant colony optimization approach to flexible protein–ligand docking. Swarm Intelligence. 1, 115134.
  14. Teng M.K., Usman N., Frederick C.A., Wang A.H. (1988) The molecular structure of the complex of Hoechst 33258 and the DNA dodecamer d (CGCGAATTCGCG). Nucl. Acids Res. 16, 2671–2690.
  15. Finlay A.C., Hochstein F.A., Sobin B.A., Murphy F.X. (1951) Netropsin, a new antibiotic produced by a Streptomyces. J. Am. Chem. Soc. 73, 341–344.
  16. Zasedatelev A.S., Borodulin V.B., Grokhovsky S.L., Nikitin A.M., Salmanova D.V., Zhuze A.L., Gursky G.V., Shafer R.H. (1995) Mono-, di- and trimeric binding of a bis-netropsin to DNA. FEBS Lett. 375, 304–306.
  17. Makarska-Bialokoz M. (2014) Fluorescence quenching effect of guanine interacting with water-soluble cationic porphyrin. J. Luminescence. 47, 27–33.

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2. Fig. 1. Formation of a hydrogen bond between benzimidazole and the AT pair (a) and benzoxazole and the GC pair of DNA (b).

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3. Fig. 2. Computer model of MBoz₂A and Hoechst 33258 complexes with d(A-T)₁₀ and d(G-C)₁₀. Atoms C (ligand) – gray, C (DNA) – gold, N – blue, O – red, H – white. Predicted hydrogen bonds are marked with a thick green line.

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4. Fig. 3. Calculated energy values ​​of MBoz₂A and Hoechst 33258 complexes with d(A-T)₁₀ and d(G-C)₁₀.

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5. Fig. 4. Synthesis of MBoz₂A, a bisbenzoxazole analogue of Hoechst 33258.

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6. Fig. 5. Changes in MBoz₂A fluorescence in the water–DMSO system. a – Fluorescence spectra upon excitation at a wavelength of 280 nm; b – fluorescence excitation spectra at a wavelength of 370 nm; c – fluorescence excitation spectra at a wavelength of 530 nm; d – fluorescence decay curves recorded through a filter transmitting light longer than 305 nm upon excitation by a pulsed LED with a wavelength of 280 nm. Empty circles – water, subsequent spectra with a step of increasing the volume fraction of DMSO by 10%, full circles – 100% DMSO. Arrows indicate the change in fluorescence intensity with an increase in the proportion of DMSO in the solution. [MBoz₂A] 10 μM, fluorescence excitation slit width 5 nm, cuvette 2 × 10 mm, room temperature (~25°C).

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7. Fig. 6. Fluorescence of MBoz₂A solvate forms in the water–DMSO system depending on the volume fraction of DMSO. a – Fluorescence lifetime of solvate forms; b – contribution of solvate forms to the total fluorescence. Empty circles – solvate form with a long fluorescence lifetime (aggregate), full circles – solvate form with a short fluorescence lifetime (monomer).

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8. Fig. 7. Circular dichroism spectra of MBoz₂A upon formation of a complex with DNA of different nucleotide composition: calf thymus DNA (a), poly(dA-dT)•poly(dA-dT) (b), poly(dG-dC)•poly(dG-dC) (c). Empty circles – DNA in the absence of ligand, full circles – maximum concentration of ligand in DNA solution. Dependence of the circular dichroism signal amplitude at a wavelength of 330 nm on the concentration of MBoz₂A (d). Empty diamonds – calf thymus DNA; filled squares – poly(dA-dT)•poly(dA-dT); filled triangles – poly(dG-dC)•poly(dG-dC); [DNA] 50 µM (bp) in 10 mM Na-phosphate buffer pH 7.0, 25°C.

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9. Fig. 8. Fluorescence spectra of MBoz₂A upon formation of complex with DNA of different nucleotide composition. Calf thymus DNA (a); poly(dA-dT)•poly(dA-dT) (b); poly(dG-dC)•poly(dG-dC) (c). Empty circles – MBoz₂A in the absence of DNA, full circles – maximum DNA concentration in the ligand solution. Dependence of MBoz₂A fluorescence intensity on DNA concentration (d). Empty symbols – fluorescence at a wavelength of 370 nm; filled symbols – fluorescence at 530 nm; circles – calf thymus DNA; squares – poly (dA-dT)•poly (dA-dT); triangles – poly(dG-dC)•poly(dG-dC); [MBoz₂A] 10 µM in 10 mM Na-phosphate buffer pH 7.0, 25°C.

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