Peptide deformylase inhibitors: a survey of the patent literature

Abstract

New antibiotics with new mechanisms of action are desperately needed, as clinically significant bacterial pathogens have not only acquired resistance to nearly all existing antibiotics, but also increasingly exhibit multi-drug resistance. Peptide deformylase (PDF), a highly conserved metalloproteinase, is an essential enzyme in the bacterial life cycle. It catalyses the removal of the terminal formyl group from the N-terminal methionine residue of the nascent bacterial polypeptide chain. Thus, inhibition of PDF, by interfering with the bacterial protein maturation process, is providing a promising new and exciting target for antibiotic therapeutic intervention without interfering with eukaryotic metabolism. Antibiotics based on PDF inhibition have the potential to provide the much needed antibacterial activity against most of the major drug-resistant pathogens and could play a significant role in the treatment of community-acquired upper respiratory tract infections. This review covers all the patenting activity in this field of research up to, and including, March 2005, and will focus on the more significant patents and patent applications.

Keywords::

• antibacterial
• hydroxamic acid
• N-formyl-hydroxylamine
• peptide deformylase (PDF)
• resistance