HACKBARTH C, LOPEZ S, WANG W, JACOBS J, JACOBS J, JAIN R, NI ZJ, TRIAS J, CHEN D, WITHERS G, PATEL DV, YUAN Z; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 228.

Versicor, Inc., Fremont, CA

Peptide deformylase (PDF) is a new target for the discovery of novel antibiotics. We have previously reported that actinonin is a naturally occurring PDF inhibitor with antibacterial activity (Chan. et al (2000) Biochemistry, 39, p 1256). New classes of PDF inhibitors were synthesized and screened against a panel of Gram positive and Gram-negative organisms in order to identify potential drug candidates [table: see text]. Based upon the screening results, several compounds with improved antibacterial activity were identified and selected for further microbiological analysis with clinical isolates of Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. MIC[90]s of these compounds against these organisms were comparable to the MICs obtained from the screening strains and cross resistance with other common antibiotics was not observed. Based on killing curves, the compounds were bacteriostatic against representative strains. Development of resistance to VRC3375 arose at a frequency of 10[-6.5] in S. aureus and 10[-8] for the three fastidious organisms evaluated. In S. aureus, these PDF inhibitors were all synergistic with erythromycin in checkerboard assays. The newer leads show improved in vitro activity in comparison to VRC3375 against Gram positive and Gram negative pathogenic microorganisms.KEYWORDS: Deformylase

Publication Types:

• Meeting Abstracts

Keywords:

• Amidohydrolases
• Anti-Bacterial Agents
• Erythromycin
• Haemophilus influenzae
• Hydroxamic Acids
• In Vitro
• Microbial Sensitivity Tests
• Moraxella (Branhamella) catarrhalis
• Proline
• Staphylococcus aureus
• Streptococcus pneumoniae
• VRC3375
• actinonin
• antagonists & inhibitors
• methods
• microbiology
• peptide deformylase

Other ID:

• GWAIDS0010837

UI: 102248335

From Meeting Abstracts