Infrared linear dichroism studies of DNA-drug complexes: quantitative determination of the drug-induced restriction of the B-A transition.
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-binding 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, FI, expressed in base pairs per added drug. Drugs with a high value of FI (more than eight base pairs per drug) were observed among both intercalating and groove-binding drugs. High values of FI imply restriction of the conformational flexibility of DNA significantly going beyond the binding site of the drug. This long-range effect of drugs on the conformational flexibility of DNA may be connected with the molecular mechanism of drug action. The freezing index FI is a new quantitative parameter of drug-DNA interaction that should be considered as a valuable tool for drug design.
Fritzsche
H
H
Department of Biophysical Chemistry, Friedrich Schiller University Jena, Germany.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D007364:Intercalating Agents / Q000494:pharmacology; D015394:Molecular Structure; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D013055:Spectrophotometry, Infrared
D000903:Antibiotics, Antineoplastic; D007364:Intercalating Agents; D004247:DNA