Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
2004-02-18
2004-09-28
Richter, Johann (Department: 1621)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C560S024000
Reexamination Certificate
active
06797730
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the use of novel antibacterial compounds, and pharmaceutical compositions containing these compounds as peptide deformylase inhibitors.
BACKGROUND OF THE INVENTION
Bacterial initiator methionyl tRNA is modified by methionyl tRNA formyltransferase (FMT) to produce formyl-methionyl tRNA The formyl methionine (f-met) is then incorporated at the N-termini of newly synthesized polypeptides. Polypeptide deformylase (PDF or Def) then deformylates primary translation products to produce N-methionyl polypeptides. Most intracellular proteins are further processed by methionine aminopeptidase (MAP) to yield the mature peptide and free methionine, which is recycled. PDF and MAP are both essential for bacterial growth, and PDF is required for MAP activity. This series of reactions is referred to as the methionine cycle (Figure 1).
Figure 1. The methionine cycle.
To date, polypeptide deformylase homologous genes have been found in bacteria, in chloroplast-containing plants, in mice and in humans. The plant proteins are nuclear encoded but appear to carry a chloroplast localisation signal. This is consistent with the observation that chloroplast RNA and protein synthesis processes are highly similar to those of eubacteria While there is limited information on protein expression of mammalian PDF gene homologs (Bayer Aktiengesellschaft, Pat. WO2001/42431), no functional role for such proteins has been demonstrated to date (Meinnel, T., Parasitology Today 16(4), 165-168, 2000).
Polypeptide deformylase is found in all eubacteria for which high coverage genonic sequence information is available. Sequence diversity among PDF homologs is high, with as little as 20% identity between distantly related sequences. However, conservation around the active site is very high, with several completely conserved residues, including one cysteine and two histidines which are required to coordinate the active site metal (Meinnel, T. et al., 1997, Journal of Molecular Biology, 267, 749-761).
PDF is recognized to be an attractive antibacterial target, as this enzyme has been demonstrated to be essential for bacterial growth in vitro (Mazel, D. et al., EMBO J. 13 (4), 914-923, 1994), is not believed to be involved in eukaryotic protein synthesis (Rajagopalan et al., J. Am. Chem. Soc. 119, 12418-12419, 1997), and is universally conserved in prokaryotes (Kozak, M., Microbiol. Rev. 47, 1-45, 1983). Therefore PDF inhibitors can potentially serve as broad spectrum antibacterial agents.
SUMMARY OF THE INVENTION
The present invention involves novel antibacterial compounds represented by Formula (1) hereinbelow and their use as PDF inhibitors.
REFERENCES:
patent: WO 02/50081 (2002-06-01), None
patent: WO 01/10834 (2001-02-01), None
Christensen, IV Siegfried B.
Lee Jinhwa
Xiang Jia-Ning
Kinzig Charles M.
McCarthy Mary
Richter Johann
Simon Soma G.
SmithKline Beecham Corporation
LandOfFree
Peptide deformylase inhibitors does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Peptide deformylase inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Peptide deformylase inhibitors will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3217331