| Abstract
| - Phosphorothioates, analogues of phosphate esters in which a sulfur replaces an oxygen atomin the phosphoryl group, are competent surrogate substrates for a number of phosphatases. Insome cases the thio analogues show similar binding (as estimated by Km) while otherphosphatases show quite different Km values for phosphate compared to phosphorothioate esters.On this basis it was hypothesized that there might be different inhibitory tendencies by thenonhydrolyzable analogues, phosphonothioic acids compared with phosphonic acids. A seriesof phosphonothioic acids and corresponding phosphonic acids were synthesized and theirinhibitory properties were compared toward human placental and E. coli alkaline phosphatases,the protein-tyrosine phosphatase from Yersinia, and the serine/threonine protein phosphatasesPP2C and lambda. Sulfur substitution for oxygen gives the phosphonothioic acids pKa valuesthat are close to those of phosphate esters, in contrast to the higher pKa values typical ofphosphonic acids. Despite different steric requirements and differences in charge distributionin the anions of phosphonothioic acids compared with phosphonic acids, it was found that,with some exceptions, differences in inhibitory properties were modest.
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