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 Kinact = 0.5 microM, 0.55 microM and 18.5 microM for bromoacetyl-, iodoacetyl- and chloroacetyl derivatives of L-2,3-diaminopropanoic acid, respectively. The inactivation obeyed the criteria for active site-directed modification.
Milewski
S
S
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, Poland.
Chmara
H
H
Andruszkiewicz
R
R
Borowski
E
E
D001667:Binding, Competitive; D002176:Candida albicans / Q000201:enzymology*; D005636:Fructosephosphates / Q000378:metabolism; D005973:Glutamine / Q000031:analogs & derivatives* / Q000378:metabolism; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors*; D007700:Kinetics; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D005636:Fructosephosphates; D005973:Glutamine; D015091:beta-Alanine; C065926:N(3)-(iodoacetyl)-2,3-diaminopropanoic acid; C072993:N(3)-(chloroacetyl)-2,3-diaminopropanoic acid; C027618:fructose-6-phosphate; C072992:N(3)-(bromoacetyl)-2,3-diaminopropanoic acid; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)