Enzymatic release of nitric oxide from -alanosine,an antineoplastic antibiotic |
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Authors: | Theodore A Alston Harold J Bright |
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Institution: | Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 USA |
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Abstract: | L-Alanosine is an antineoplastic drug which is the 3-isonitramino analog of -aspartic acid. The drug is known to be metabolized to the corresponding 2-oxo acid. Unlike the parent amino acid, the 2-oxo acid is unstable under mild conditions. When the 2-oxo acid is generated by the aerobic action of -amino acid oxidase on -alanosine, the reaction mixture contains products capable of diazotizing sulfanilamide and of reducing ferricytochrome to ferrocytochrome . It is thus likely that, as expected from model reactions, the unstable 2-oxo acid derived from -alanosine decomposes into nitric oxide and other reactive free-radical species. Enzymatically promoted production of highly cytotoxic nitric oxide may pertain to the biological activity of the antibiotic. The reaction should prove extrapolable to the design of other enzyme-activated cytotoxic agents. |
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