Double helix Drugs

Double helix (DNA), 1103-1105 Doublet (NMR), 462 Dovvnfield (NMR), 445 Drugs, approval procedure for, 165 chiral, 320-322 origin of, 164... 

Mitomycin C, 1, is a potent antitumor antibiotic discovered by Japanese scientists in fermentation cultures of Streptomyces caespitosus. It has been described as "small, fast and deadly (but very selective)" and has an extraordinary ability to crosslink the complementary strands of the DNA double helix with high efficiency and absolute specificity. It is so lethal that one crosslink per genome is sufficient to cause death of a bacterial cell. Mitomycin C, which is widely used clinically as an antitumor drug, does not react with DNA, but enzymatic reduction of the quinone induces a cascade of transformations which results, ultimately, in formation of the DNA crosslink 2. 

Domoic acid 535-536 Donor substrate 373 Dopamine 519 Double helix 417, e210 Drinking Water Directive 311 Drosophila 322 AChE 314 melanogaster 314 wild-type enzyme 314 Drug 418... 

Other drugs classified as plant alkaloids include etoposide, irinotecan, teniposide, and topotecan (see Table 36 1). These drugs inhibit specific enzymes known as topoisomerase enzymes, which are necessary for DNA replication.11 Inhibition of these enzymes causes a break in both strands of the DNA double helix, which leads to DNA destruction and cell death. Etoposide and teniposide inhibit the topoisomerase I form of this enzyme, and irinotecan and topotecan inhibit the topoisomerase II form of this enzyme. These drugs are therefore used to limit cell division and cancer growth in various types of neoplastic disease (see Table 36-4). 

The drug binds to DNA by intercalation between adjacent base pairs of the double helix, thus inhibiting RNA synthesis.2... 

From these experiments it can be concluded that the closure of the monofunctional adducts depends upon the presence of other adducts in its vicinity. Although a systematic study has not yet been done, the interference between two or more adducts is expected to be a function of several parameters, such as the nature and the number of base pairs between the adducts, the DNA supercoiling, the local environment of the DNA, in addition to the distortions of the DNA double helix induced by the adducts, which are also function of these parameters. DNA has to be platinated at a low drug-to-nucleotide residue ratio when in vitro and in vivo experiments are compared. This holds also for cisplatin-modified DNA, but is masked by the preferential binding of cisplatin to runs of guanine residues and the ability of the monofunctional adducts to react with the adjacent residues. 

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