Synthesis and evaluation of new 4-phospho-D-erythronic acid derivatives as competitive inhibitors of spinach ribose-5-phosphate isomerase

This paper reports the synthesis of new 4-phospho-D-erythronic acid derivatives, namely 4-phospho-D-erythronohydroxamic acid (1), 4-phospho-D-erythronohydrazide (2), and 4-phospho-D-erythronamide (3), and their kinetic evaluation as new competitive inhibitors of the isomerization reaction between D-ribose 5-phosphate and D-ribulose 5-phosphate catalyzed by spinach ribose-5-phosphate isomerase (RPI). By comparison to the only known RPI inhibitor, 4-phospho-D-erythronate (4, K_i=28μM, K _m/K_i=270), the hydroxamic acid 1, obtained by an eight-step synthesis from D-arabinose, appears as a new potent high-energy intermediate analogue inhibitor of the isomerization reaction (K _i=29μM, K_m/K_i=260).