Chromomycin A3 (CHR) binding to the duplex d(CAAGTCTGGCCATCAGTC)- d(GACTGATGGCCAGACTTG) has been studied using quantitative footprinting methods. Previous NMR studies indicated CHR binds as a dimer in the minor groove. Analysis of autoradiographic spot intensities derived from DNase I cleavage of the 18-mer in the presence of various amounts of CHR revealed that the drug binds as a dimer to the sequence 5’-TGGCCA-3’, 3’-ACCGGT-5’ in the 18-mer with a binding constant of (2.7 f 1.4) X lo7 M-l. Footprinting and fluorescence data indicate that the dimerization constant for the drug in solution is -lo5 M-l. Since it has been suggested that CHR binding alters DNA to the A configuration, quantitative footprinting studies using dimethyl sulfate, which alkylates at N-7 of guanine in the major groove, were also carried out. Apparently, any drug-induced alteration in DNA structure does not affect cleavage by DMS enough to be observed by these experiments.
Stankus, A., Goodisman, J., & Dabrowiak, J. C. (1992). Quantitative footprinting analysis of the chromomycin A 3-DNA interaction. Biochemistry, 31(38), 9310-9318.
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