The non-covalent interaction of pyrrolo[2, 1-c] [1, 4]benzodiazepine-5, 11-diones with DNA.

Published

Journal Article

A series of 15 pyrrolo[2, 1-c] [1, 4]benzodiazepine-5, 11-diones has been synthesized and evaluated for in vitro DNA binding by thermal denaturation and fluorescence quenching studies with calf thymus (CT) DNA. The results indicate that two compounds of the series, 7 and 8, elevate the melting point of DNA by 2.9 +/- 0.6 and 3.3 +/- 0.8 K, respectively. Similarly, a significant quenching of the fluorescence of the dihydroxy analogue 8 was observed upon interaction with CT-DNA. As controls, the dihydroxy isomer 9 with the reverse stereochemistry at C2 and the non-substituted parent dilactam 12, failed to increase the DNA melting point or exhibit significant quenching upon interaction with DNA. In addition, preliminary experiments with GC- and AT-rich polymers suggest some sequence-dependent properties for dilactams 7 and 8. Overall, these results indicate a highly specific structural requirement for DNA binding. Molecular modelling with d(GTAGATC), d(GCAGATC) and d(GCGTAGC) duplex sequences has provided a model based on hydrogen bonding between the dihydroxy dilactam 8 and DNA, that rationalizes some of the results obtained. It is possible that the observed interactions represent the non-covalent (binding) component of the interaction of covalently-bonding anthramycin-type anti-tumour antibiotics with DNA.

Full Text

Duke Authors

Cited Authors

  • Jones, GB; Davey, CL; Jenkins, TC; Kamal, A; Kneale, GG; Neidle, S; Webster, GD; Thurston, DE

Published Date

  • August 1990

Published In

Volume / Issue

  • 5 / 3

Start / End Page

  • 249 - 264

PubMed ID

  • 2400538

Pubmed Central ID

  • 2400538

Electronic International Standard Serial Number (EISSN)

  • 1460-2148

International Standard Serial Number (ISSN)

  • 0266-9536

Language

  • eng