The lysine pathway as a target for a new genera of synthetic antibacterial antibiotics?
Unsaturated analogues of diaminopimelic acid have been synthesized. The amino acids were designed so that they would be reversible or irreversible inhibitors of both of the two last enzymes of the lysine pathway. The compounds were tested with meso-diaminopimelate decarboxylase. trans-3,4-Didehydrodiaminopimelic acid (2) was found to be the most potent inhibitor. The antibacterial activities did not correlate with enzyme inhibiting activities. 4-Methylenediaminopimelic acid 4 showed strong antibacterial properties. It is suggested that L,L-diaminopimelate epimerase could be the target enzyme.
D000591:Amino Acid Isomerases; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001426:Bacterial Proteins; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives; D008239:Lysine / Q000378:metabolism*; D019998:Racemases and Epimerases / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003960:Diaminopimelic Acid; D002262:Carboxy-Lyases; C079912:LysA protein, Bacteria; C020031:diaminopimelic acid decarboxylase; D019998:Racemases and Epimerases; D000591:Amino Acid Isomerases; C042032:diaminopimelate epimerase; D008239:Lysine