Hydrogen bonding, overlap geometry, and sequence specificity in anthracycline antitumor antibiotic.DNA complexes in solution.
- 1 June 1981
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 78 (6) , 3333-3337
- https://doi.org/10.1073/pnas.78.6.3333
Abstract
Structural aspects of the intercalation complex of the anthracycline antitumor antibiotic daunomycin and its analogs with the synthetic DNA poly(dA-T) were deduced by 1H and 31P NMR in high-salt solution. The base pairs are intact at the antibiotic binding site; the anthracycline phenolic hydroxyls form intramolecular H bonds with the quinone carbonyls and are shielded from solvent in the intercalation complex. The complexation shifts of the exchangeable phenolic and nonexchangeable aromatic protons demonstrate that rings B and C of the anthracycline chromophore overlap with adjacent base pairs; anthracycline ring D passes right through the intercalation site in the complex. Two resolved 31P resonances attributable to the dA-dT and dT-dA phosphodiester linkages in the P spectra of the neighbor-exclusion daunomycin.cntdot.poly(dA-dT) complex were observed. The anthracycline antitumor antibiotic apparently exhibits a sequence specificity in its intercalation complex with alternating purine-pyrimidine synthetic DNA in solution. These conclusions on H bonding and overlap geometry at the intercalation site and sequence specificity for the daunomycin.cntdot.poly(dA-dT) complex in solution are in agreement with the structure of the daunomycin.cntdot.dC-dG-dT-dA-dC-dG hexanucleotide duplex crystalline complex at atomic resolution published recently.This publication has 22 references indexed in Scilit:
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