Deoxyribonucleic acid alkylation

Chemotherapeutic agents are grouped by cytotoxic mechanism. The alkylating agents, such as cyclophosphamide [50-18-0] and melphalan [148-82-3] interfere with normal cellular activity by alkylation deoxyribonucleic acid (DNA). Antimetabohtes, interfering with complex metaboHc pathways in the cell, include methotrexate [59-05-2] 5-fluorouracil [51-21-8] and cytosine arabinoside hydrochloride [69-74-9]. Antibiotics such as bleomycin [11056-06-7] and doxombicin [23214-92-8] h.a.ve been used, as have the plant alkaloids vincristine [57-22-7] and vinblastine [865-21-4]. 

Ti values may occur with such native biopolymers as ribonuclease A, deoxyribonucleic acid, and collagen, whose molecular motions are restricted, but, as yet, high values have not been observed for polysaccharides in solution, or for gels, in which these motional-restriction effects may be equivalent, or less marked. However, an extensive relaxation-study by Levy and coworkers68 on poly(n-alkyl methacrylates) may serve as a model for future experiments on polysaccharides, as this type of molecule has a main chain and side chains, albeit more mobile than those in polysaccharides. 

In animals, there is some evidence that hexachlorobutadiene interacts with genetic material. Male rats administered a single gavage dose of hexachlorobutadiene (20 mg/kg/day) showed a 40% increase in renal deoxyribonucleic acid (DNA) repair and 0.78 alkylations per million nucleotides... 

One very important alkylation reaction is the Friedel-Crafts alkylation reaction, used for the alkylation of aromatic species, which was discovered in 1877. Alkylation is used industrially to produce basic building blocks for the synthesis of more elaborate materials. One commonly used application is in the production of antiknock gasoline. In medicine, alkylation of deoxyribonucleic acid (DNA) is used in chemotherapy to damage the DNA of cancer cells. In this section, the three principle types... 

Cradiom, A.R. and J.J. Roberts. 1966. Mechanism of the cytotoxic action of alkylating agents in mammaUan cells and evidence for die removal of alkylated groups from deoxyribonucleic acid. Nature (Lond) 211 150-153. 

Ethylene oxide (bp, 10.8°C) is a gaseous alkylating agent. It alkylates proteins and ribonucleic and deoxyribonucleic acid in micro-organisms. It replaces labile hydrogen with hydroxyethyl groups. Ethylene oxide is utilized as a surface sterilant. Bulk crystalline materials can occlude vegetative bacterial cells or spores with crystals. Consequently, ethylene oxide does not reach them. The final step prior to sterilization is an aseptic recrystallization step. 

Mustard also has cholinergic action stimulating both muscarinic and nicotinic receptors.33 Alkylation of Deoxyribonucleic Acid... 

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