Amide and ester derivatives of N3-trans-epoxysuccinoyl-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.
Andruszkiewicz
R
R
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, Poland.
Milewski
S
S
Borowski
E
E
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000599:Amino Acids, Diamino / Q000138:chemical synthesis / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors*; D010455:Peptides; D011422:Propionates / Q000138:chemical synthesis* / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D000577:Amides; D000599:Amino Acids, Diamino; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D004952:Esters; D005656:Fungal Proteins; D010455:Peptides; D011422:Propionates; C055110:N-L-alanyl-3-(((3-(aminocarbonyl)oxiranyl)carbonyl)amino)-L-alanine; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)