N3-HALOACETYL DERIVATIVES OF L-2,3-DIAMINOPROPANOIC ACID - NOVEL INACTIVATORS OF GLUCOSAMINE-6-PHOSPHATE SYNTHASE

N3-Haloacetyl derivatives of L-2,3-diaminopropanoic acid, novel glutamine analogs, were shown to be strong inhibitors of glucosamine-6-phosphate synthase from bacteria and Candida albicans. The inhibition was competitive with respect to glutamine and non-competitive with respect to D-fructose-6-phosphate. In the absence of glutamine, the tested compounds inactivated glucosamine-6-phosphate synthase from C. albicans with K(inact) = 0.5-mu-M, 0.55-mu-M and 18.5-mu-M for bromoacetyl-, iodoacetyl- and chloroacetyl derivatives of L-2,3-diaminopropanoic acid, respectively. The inactivation obeyed the criteria for active site-directed modification.