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Nucleic Acids Research, 1994, Vol. 22, No. 5 787-791
© 1994

STRUCTURAL BIOLOGY

Infrared linear dichroism studies of DNA-drug complexes: quantitative determination of the drug-induced restriction of the B - A transition

Hartmut Fritzsche

Department of Biophysical Chemistry, Institute of Molecular Biology, Friedrich Schiller University Jena D-07708 Jena, Germany

Received November 30, 1993. Revised January 31, 1994. Accepted January 31, 1994.

The B - A transition of films or fibers of NaDNA occurs at a relative humidity of 75 – 85%. The fraction of DNA that changed the conformation from B to A form can be determined quantitatively by Infrared linear dichroism. DNA-bindlng drugs can ‘freeze’ a fraction of DNA in the B form. This fraction of DNA is in the B form and cannot be converted to A-DNA even at a reduced relative humidity of 54%. The ‘freezing’ potentiality of various drugs can be described by the ‘freezing’ Index, Fl, expressed in base pairs per added drug. Drugs with a high value of Fl (more than eight base pairs per drug) were observed among both intercalating and groove-binding drugs. High values of Fl imply restriction of the conformatlonal flexibility of DNA significantly going beyond the binding site of the drug. This long-range effect of drugs on the conformatlonal flexibility of DNA may be connected with the molecular mechanism of drug action. The freezing index Fl is a new quantitative parameter of drug - DNA interaction that should be considered as a valuable tool for drug design.


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