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Nucleic Acids Research, 1983, Vol. 11, No. 10 3411-3430
© 1983

CHEMISTRY

Anthracycline-binding induced Dna stiffenin, bending and elongation; stereochemical implications from viscometic investigations

K.E. Reinert

Academy of Sciences of the GDR Central Institute of Microbiology and Experimental Therapy, Department of Biophysical Chemistry DDR-69 Jena, Beutenbergstr. 11, GDR

Received January 6, 1983. Revised March 24, 1983. Accepted April 22, 1983.

Upon interaction of the three anthracycline antibiotics dau-nomycin, adriamyoin, and aclacinomyoin A with calf thymus DNA the relative changes of both DNA contour length, {bigtriangleup}*L/Lo, and persistence length, {bigtriangleup}a/ao, have been determined as a function of r, the ratio of bound ligand molecules per DNA mononuoleotide. Prom the r dependence of {bigtriangleup}a/ao a measure for the stiffening effect and n also the angle 7camma; of ligand-induced DNA bending could be derived. Experimental basis are titration viscometric measurements upon both low and high molecular weight DNA.

It was found that the DNA contour length increases linearly with r by approximately 0.34 nm per bound drug molecule. The comparatively very high DNA stiffening effect measured in solution is understandable as a result of helix clamping by at least two anthracyoline groups of sufficient long distance. The variation of J" on DNA interaction with different anthracycline derivatives find their explanation in terms of different values of the mismatch to in-register binding prior to complex formation.

Prom an analogous interpretation of viscosity measurements by Arcamone and coworkers upon high molecular weight DNA with many anthracycline derivatives18"it can be concluded that DNA interaction by both amino sugar and 9-acetyl group are responsible for the generation of strong anthracycline binding mediated DNA stiffening effects in solution.

(A combined analysis of the viscosity measurements by Cohen Eisenberg44 and Armstrong et al.43 upon DNA interaction withpro-flavine indicates a very small DNA stiffening effect, j*-6.7o and a helix elongation by 0.35 nm per bound ligand molecule


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