[Peptide-deformylase inhibitors, a new class of antibiotics].
PEPTIDE-DEFORMYLASE: During protein synthesis in bacteria, a transformylase coding the fmt gene provides a formyl group on methionine before binding to the ARNm-ARNt complex. This tormylated methionine initiates the protein synthesis. The adjunction of an amino acid to the peptide chain leads to a peptide associated with a formylated methionine. The final stage requires a metallo-enzyme, peptide deformylase, which releases the peptide and regenerates the methionin. PEPTIDE-DEFORMYLASE INHIBITORS (PDF): Often rejected by the efflux pumps of Gram negative bacteria, PDF inhibitors are administered in the form of pro-drugs, capable of acting even in the bacteria that have lost their transformylase gene. TWO PRODUCTS: These are VCR 4887 developed by Versicor and Novartis and BB 83698 developed by British Biotechnology Genesoft. They are presently in the process of clinical predevelopment. They represent an important innovation and widen the range of new antibiotic classes.
Dubreuil
Luc
L
Laboratoire de Microbiologie, Faculté de pharmacie, 3, rue du Pr Laguesse, BP 83, 59006 Lille. ldubreuil@phare.univ-lille2.fr
D000581:Amidohydrolases; D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008715:Methionine / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D008715:Methionine; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase