Dubreuil Luc
Laboratoire de Microbiologie, Faculté de pharmacie, 3, rue du Pr Laguesse, BP 83, 59006 Lille.
Presse Med. 2002 Nov 30;31(38):1810-2.
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.
在细菌蛋白质合成过程中，编码fmt基因的转甲酰酶在与mRNA - tRNA复合物结合之前，为甲硫氨酸提供一个甲酰基。这种甲酰化甲硫氨酸启动蛋白质合成。氨基酸连接到肽链上会产生一个与甲酰化甲硫氨酸相关的肽。最后阶段需要一种金属酶——肽脱甲酰基酶，它释放肽并使甲硫氨酸再生。肽脱甲酰基酶抑制剂（PDF）：PDF抑制剂常被革兰氏阴性菌的外排泵排出，以前药形式给药，即使在已失去转甲酰酶基因的细菌中也能发挥作用。两种产品：分别是Versicor和诺华公司研发的VCR 4887以及英国生物技术基因软件公司研发的BB 83698。它们目前正处于临床前开发阶段。它们代表了一项重要的创新，拓宽了新型抗生素类别的范围。
