Antineoplastic agents enzymes

Antineoplastic agent Enzyme inhibitors Trypanocidal agent... 

Antineoplastic agents that cannot be grouped under subheadings 1-9 include miltefosine which is an alkylphosphocholine that is used to treat skin metastasis of breast cancer, and crispantase which breaks down asparagine to aspartic acid and ammonia. It is active against tumor cells that lack the enzyme asparaginase, such as acute lymphoblastic leukemia cells. Side effects include irritation of the skin in the case of miltefosine and anaphylactic reactions in the case of crispantase. Another recent development is the proteasome inhibitor bortezomib which is used to treat multiple myeloma. 

The epidermal growth factor receptor 2 (HER-2) is a protein found on the surface of cells. Heterodimerization of HER-2 activates the enzyme tyrosine kinase, triggering reactions that cause the cells to grow and multiply. HER-2 is found at abnormally high levels on the surface of many types of cancer cells, which may divide excessively. Antibodies targeting HER-2 (e.g., trastuzumab) are used as antineoplastic agents. 

Other Copper Oxidases. A number of additional multicopper oxidases have been detected [22], including phenoxazinone synthase (Table 1). This enzyme catalyzes the overall six-electron oxidative coupling of 2-aminophenols to form 1-aminophenoxazinone, the final step in the bacterial (Streptomyces) biosynthesis of the antineoplastic agent actinomycin. 

Glycinamide ribonucleotide transformy-lase (GAR TFase) catalyzes the transfer of a formyl group from JV -formyltetrahydrofo-late to glycinamide ribonucleotide (Equation 17.37). This is a crucial step in de novo purine biosynthesis, which is essential for cell division, and GAR TFase has become a target enzyme for the development of antineoplastic agents. 

Antihistamines Enzymes and digestive aids Antineoplastic agents... 

The derivative 147 of camptothecin 146, naturally occurring antineoplastic agent, stabilizing the enzyme-mediated DNA cleavage, has been tritium-labelled at C,5) position by a three-step sequence starting from 5)-10-hydroxycamptothecin in order to investigate whether the presence of a peripheral electrophilic substituent in 147 renders the reversible binding of 146 with DNA-topoisomerase I covalent complex irreversible . ... 

The blue oxidases-related enzymes include phenoxazinone synthase from S. antibioticus This enzyme is a copper-containing oxidase that catalyzes the coupling of 2-aminophenols to form the 2-aminophenoxazinone chromophore. This reaction constitutes the final step in the biosynthesis of the potent antineoplastic agent actinomycin. The crystal structure of the oxidized form phenoxazinone synthase from S. anibioticus has been determined. It has been solved in his hexameric form. One monomer is very similar to Iaccase or ascorbate oxidase but it contains a long loop, which connects two domains and stabilizes the hexameric structure. Bound... 

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