The origin of the DNA induced circular dichroism of CC-1065 and analogs.
The calf thymus DNA (CT-DNA) and poly(dI-dC).poly(dI-dC) binding properties of the natural antitumor antibiotic CC-1065 and selected analogs of CC-1065 were studied by circular dichroism (CD) and absorbance methods. The results indicate that the intense long wavelength DNA-induced CD band of these molecules originates from a chiral electronic transition which is delocalized over the whole molecule. Both the covalently bound species (N-3 adenine adduct) and the reversibly bound species exhibit the characteristic spectral behavior of an inherently dissymmetric chromophore when these agents bind within the minor groove of B-form DNA. This mechanism of optical activity accounts for why CC-1065 shows a weak CD in buffer but a very intense induced CD at long wavelength when bound to DNA, why the intensity of the induced CD of CC-1065 analogs depends upon how many fused ring systems the analog contains, and why covalently bound analogs having the mirror image configuration of the natural configuration also exhibit an intense positive induced CD band at long wavelength.
Krueger
W C
WC
Physical and Analytical Chemistry, Upjohn Company, Kalamazoo, MI 49001.
Prairie
M D
MD
D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D001665:Binding Sites; D002942:Circular Dichroism; D004247:DNA / Q000494:pharmacology*; D000080890:Duocarmycins; D007211:Indoles; D007933:Leucomycins / Q000737:chemistry*; D008968:Molecular Conformation; D013302:Streptomyces / Q000032:analysis
D000903:Antibiotics, Antineoplastic; D000080890:Duocarmycins; D007211:Indoles; D007933:Leucomycins; C018782:CC 1065; D004247:DNA