Arsonates as Analogues of Nonphosphate Metabolites

Phosphonates have been widely used as analogues of carboxylic acids. They have been particularly effective as analogues of tetrahedral transition states that occur in the course of enzyme-catalyzed reactions such as hydrolysis of the amide (peptide) bond. As such, they may be used as inhibitors of enzymes (e.g., 82, 83) or as haptens for producing antibodies that are catalytic (e.g., 84). A notable example is H203P— CH2—CH2—CH(—NH2)—COOH, which has effects that are likely to be due to its interference with glutamate as a neurotransmitter (85). 

The malate, oxaloacetate, and fumarate analogues 3-arsonolactate (86), 3-arsonopyruvate (68), and CE)-3-arsonoacrylate (87,88) have been made Ali and Dixon (88) found that the fumarate and malate analogues were not substrates for fumarate hydratase, but competitive inhibitors, arsonoacrylate, H203As—CH=CH—COOH, with fumarate ( / 1.8) and arsonolactate, H203As—CH2—CHOH—COOH, with malate (KJKm 1.6). Incidentally, although phosphonopyruvate is a poor substrate for malate dehydrogenase (89,90), 3-(hydroxyphosphinoyl)pyru-vate, HO—P(H)(0)—CH2—CO—COOH, is much better (89). It proved impossible to show the reverse reaction with arsonolactate (89, 91). 

Arsonoalanine was not a substrate or inhibitor of aspartate aminotransferase under the conditions tested (88), but it inactivated it progressively. Many alanine derivatives in which there is a good leaving group on C-3 do this (95-97), both to this enzyme and other pyridoxal enzymes (96), with some interesting results, e.g., the difference in reac- 

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B. Comparison of Arsonates with Phosphonates Arsonates as Analogues of Nonphosphate Metabolites Other Biological Actions of Arsonates... 

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