Structure-activity relationship analysis and therapeutic potential of peptide deformylase inhibitors.
Peptide deformylase inhibitors (PDFIs) appear to be one of the most exciting classes of antibacterial agents discovered to date. Rapid progress in the development of PDFIs has been possible because peptide deformylase is a metalloprotease, and this class of enzymes shows a high degree of structure-function conservation, and because the most potent PDFIs are hydroxamate derivatives, a well known category of pharmacophores. The current challenge in structure-activity relationship analysis is obtaining molecules with potent in vivo antibacterial activity against a range of drug-resistant pathogens. The PDFIs currently in clinical trials target community-based bacterial infections, with a potential major pharmaceutical market.
Boularot
Adrien
A
Centre National de la Recherche Scientifique, Protein Maturation Group, Institut des Sciences du Végétal, UPR2355, Bâtiment 23, 1 avenue de la Terrasse, F-91198 Gif-sur-Yvette, France.
Giglione
Carmela
C
Artaud
Isabelle
I
Meinnel
Thierry
T
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D000581:Amidohydrolases; C084507:peptide deformylase