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Variation in the inhibition of restriction enzyme cleavage of lambda phage DNA produced by two covalent binding antitumor agents: Anthramycin and mitomycin C
Authors:David J. Kaplan
Affiliation:Division of Medicinal Chemistry and Pharmacognosy College of Pharmacy University of Kentucky Lexington, Kentucky 40536-0053 U.S.A.
Abstract:DNA-drug complexes containing various levels of covalently bound mitomycin C (MC) or anthramycin were subjected to the actions of a number of restriction enzymes. While MC presented only a partial block to the actions of a number of these enzymes, anthramycin, at high binding ratios, blocked enzymatic activity very well. The contrast seen in the restriction cleavage of these DNA-drug complexes may be related to the different points of attachment in DNA (minor groove vs. major groove) for these drugs. Although similarities in electrophoretic band patterns exist for both drug complexes, certain differences are indicative of preferences in binding sequences that these drugs may have for DNA. The results show that these sequences do not necessarily lie immediately within the restriction cut sites but may effect the cutting of these sites from a distance. The results also further support anthramycin's potential usage as a selective/reversible blocking agent for recombinant research.
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