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. 1988 Apr 11;16(7):3061–3073. doi: 10.1093/nar/16.7.3061

Energetics and stereochemistry of DNA complexation with the antitumor AT specific intercalators tilorone and m-AMSA.

K X Chen 1, N Gresh 1, B Pullman 1
PMCID: PMC336452  PMID: 3368315

Abstract

Computations by the SIBFA method on the intercalative interaction energies of tilorone and m-AMSA with B-DNA representative oligonucleotides account for the specificity of these antitumor drugs for AT sites and minor groove intercalation. In tilorone this specificity is due to the strong preference of the side chains for the minor groove, which overcomes the preference of the chromophore for a GC intercalation site. In m-AMSA the specificity is due to the combined preference of both the chromophore and the anilino side chain for AT intercalation site and minor groove, respectively. o-AMSA is shown to manifest a similar (although significantly less pronounced specificity) as m-AMSA but a higher affinity for DNA. A comparison of the energetics and stereochemistry of intercalative binding to DNA of m-AMSA (AT minor groove specific) and 9-aminoacridine-4-carboxamide (GC major groove specific), which possess the same chromophore and differ only by the nature and position of the side chains, shows the possibility of important variations in the intercalative behaviour of chromophoric drugs as a function of the substituent groups attached to them.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chandra P., Woltersdorf M. Influence of tilorone and cogeners on the secondary structure and template activity of DNA. FEBS Lett. 1974 Apr 15;41(1):169–173. doi: 10.1016/0014-5793(74)80980-4. [DOI] [PubMed] [Google Scholar]
  2. Chen K. S., Gresh N., Pullman B. A theoretical investigation on the sequence selective binding of adriamycin to double-stranded polynucleotides. Nucleic Acids Res. 1986 Mar 11;14(5):2251–2267. doi: 10.1093/nar/14.5.2251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen K. X., Gresh N., Pullman B. A tentative model of the intercalative binding of the neocarzinostatin chromophore to double-stranded tetranucleotides. Nucleic Acids Res. 1987 Mar 11;15(5):2175–2189. doi: 10.1093/nar/15.5.2175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen K. X., Gresh N., Pullman B. A theoretical investigation on the sequence selective binding of daunomycin to double-stranded polynucleotides. J Biomol Struct Dyn. 1985 Dec;3(3):445–466. doi: 10.1080/07391102.1985.10508434. [DOI] [PubMed] [Google Scholar]
  5. Chen K. X., Gresh N., Pullman B. A theoretical investigation on the sequence selective binding of mitoxantrone to double-stranded tetranucleotides. Nucleic Acids Res. 1986 May 12;14(9):3799–3812. doi: 10.1093/nar/14.9.3799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen K. X., Gresh N., Pullman B. A theoretical study of anthracene and phenanthrene derivatives acting as A-T specific intercalators. Nucleic Acids Res. 1986 Nov 25;14(22):9103–9115. doi: 10.1093/nar/14.22.9103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen K. X., Gresh N., Pullman B. Groove selectivity in the interaction of 9-aminoacridine-4-carboxamide antitumor agents with DNA. FEBS Lett. 1987 Nov 30;224(2):361–364. doi: 10.1016/0014-5793(87)80485-4. [DOI] [PubMed] [Google Scholar]
  8. Lee J. S., Waring M. J. Interaction between synthetic analogues of quinoxaline antibiotics and nucleic acids. Changes in mechanism and specificity related to structural alterations. Biochem J. 1978 Jul 1;173(1):129–144. doi: 10.1042/bj1730129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Low C. M., Olsen R. K., Waring M. J. Sequence preferences in the binding to DNA of triostin A and TANDEM as reported by DNase I footprinting. FEBS Lett. 1984 Oct 29;176(2):414–420. doi: 10.1016/0014-5793(84)81209-0. [DOI] [PubMed] [Google Scholar]
  10. Miller K. J. Interactions of molecules with nucleic acids. I. An algorithm to generate nucleic acid structures with an application to the B-DNA structure and a counterclockwise helix. Biopolymers. 1979 Apr;18(4):959–980. doi: 10.1002/bip.1979.360180415. [DOI] [PubMed] [Google Scholar]
  11. Pullman A., Pullman B. Molecular electrostatic potential of the nucleic acids. Q Rev Biophys. 1981 Aug;14(3):289–380. doi: 10.1017/s0033583500002341. [DOI] [PubMed] [Google Scholar]
  12. Viswamitra M. A., Kennard O., Cruse W. B., Egert E., Sheldrick G. M., Jones P. G., Waring M. J., Wakelin L. P., Olsen R. K. Structure of TANDEM and its implication for bifunctional intercalation into DNA. Nature. 1981 Feb 26;289(5800):817–819. doi: 10.1038/289817a0. [DOI] [PubMed] [Google Scholar]
  13. Wakelin L. P., Atwell G. J., Rewcastle G. W., Denny W. A. Relationships between DNA-binding kinetics and biological activity for the 9-aminoacridine-4-carboxamide class of antitumor agents. J Med Chem. 1987 May;30(5):855–861. doi: 10.1021/jm00388a019. [DOI] [PubMed] [Google Scholar]
  14. Wilson W. R., Baguley B. C., Wakelin L. P., Waring M. J. Interaction of the antitumor drug 4'-(9-acridinylamino)methanesulfon-m-anisidide and related acridines with nucleic acids. Mol Pharmacol. 1981 Sep;20(2):404–414. [PubMed] [Google Scholar]
  15. Wright R. G., Wakelin L. P., Fieldes A., Acheson R. M., Waring M. J. Effects of ring substituents and linker chains on the bifunctional intercalation of diacridines into deoxyribonucleic acid. Biochemistry. 1980 Dec 9;19(25):5825–5836. doi: 10.1021/bi00566a026. [DOI] [PubMed] [Google Scholar]

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