Phosphosulfate linkage

The activation mechanism of phosphosulfate linkages (P—O —S)has been studied to understand the chemistry of biological sulfate-transfer reactions of phosphosul-fates of adenosine (APS and PAPS). Several phosphosul-fates were prepared and subjected to several nucleophilic reactions including hydrolysis. In general, phosphosulfates are stable in neutral aqueous mediay but become labile under acidic conditions, resulting in selective S—O fission. This S—O fission appears to occur by unimolecular elimination of sulfur trioxide, which can react with a nucleophilic acceptor, leading to a sulfate-transfer reaction. This process can be accelerated by Mg2+ ion when the solvent is of low water content. Under neutral conditions, divalent metal ions also were found to catalyze nucleophilic reactions, but these occurred on phosphorus to result in exclusive P-O fission. 

As described above, the phosphosulfate linkage is acid labile but stable under neutral conditions. We, therefore, directed our next efforts to activating it under neutral conditions, whatever the site of bond fission. One obvious way was to use metal ions. However, it was evident that the effect of metal ion alone was small. Therefore, we examined the effects of amines that might act as nucleophiles cooperatively with metal ion. 

In support of its role as an intermediate in purine metabolism, adenylosuccinic acid has been isolated from mammalian liver (164) and from Penidllium chrysogenum (166). The free base, adeninosuccinic acid [6-(succinoamino) purine], was identified in human urine (166) and isolated from Neurospora mutants (167, 168). Also, the ribonucleoside derivative of adeninosuccinic acid (adeno lsuccinic acid) has been found in human cerebrospinal fluid (169) and in a Neurospora mutant (168). Another adenylosuccinate compound contained sulfate in a ribos fi -phosphosulfate linkage as well as a peptide residue, but its significance is not known (160). 

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