INFRARED LINEAR DICHROISM STUDIES OF DNA DRUG COMPLEXES - QUANTITATIVE-DETERMINATION OF THE DRUG-INDUCED RESTRICTION OF THE B-A TRANSITION

被引:15
作者
FRITZSCHE, H
机构
[1] Department of Biophysical Chemistry, Institute of Molecular Biology, Friedrich Schiller University Jena
关键词
D O I
10.1093/nar/22.5.787
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:787 / 791
页数:5
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