AMIDE AND ESTER DERIVATIVES OF N-3-TRANSEPOXYSUCCINOYL-L-2,3-DIAMINOPROPANOIC ACID - INHIBITORS OF GLUCOSAMINE-6-PHOSPHATE SYNTHASE

Several analogs 5, 6, 7, 8, 10 and 11 of the C-terminal fragment of a peptide antibiotic Sch 37137 were designed and tested as inhibitors of glucosamine-6-phosphate synthase from Saccharomyces cerevisiae. From IC50 values and kinetic parameters of inhibition of glucosamine-6-phosphate synthase by compounds 5-11 it has been found that the inhibitory potency of these compounds follows the order: 6 > 5 > 8 > 9 > 7, 10, 11. This suggests that an inhibitor with a primary amido group binds better to the active site of the enzyme than other inhibitors. The order of reactivity of compounds 5-11 may be attributed to a steric inability of the inhibitor to fit into the active site of the enzyme and also indicates the importance of the chirality of trans-epoxysuccinic acid on the inhibitory properties of the synthesized compounds.