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Nucleic Acids Research, 1988, Vol. 16, No. 9 3907-3918
© 1988

Articles

DNA unwinding and inhibition of T4 DNA ligase by anthracyclines

Alessandra Montecucco, Guido Pedrali-Noy, Silvio Spadari, Elisabetta Zanolin and Giovanni Ciarrocchi*

Istituto di Genetica Biochimica ed Evoluzionistica CNR, 27100 Pavia, Italy

* To whom correspondence and reprints request should be addressed

Received December 29, 1987. Revised March 1, 1988. Accepted March 1, 1988.

The ability to alter DNA tertiary structure of ten anthracycline derivatives whose antitumor potency is known was studied by an assay that makes use of nicked circular DNA and bacteriophage T4 DNA ligase. This assay allows the detection of tertiary structure alterations caused by DNA binding of both intercalating and non-intercalating drugs. The determination of these events can be obtained at different temperatures in the range of activity of DNA ligase. The results indicate that anthracyclines alter the DNA tertiary structure but this property does not correlate with their cytotoxic or antitumor activities. An additional interesting finding was that several anthracyclines inhibit T4 DNA ligase. The inhibition can be complete and is a cubic function of drug concentration. The inhibition of DNA ligase does not correlate with the ability of anthracyclines to alter the tertiary structure of DNA but is dependent from the presence of an amino group on the sugar ring.


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