Bioorg Med Chem Lett. 2004 Mar 22;14(6):1477-81.

Identification of novel potent bicyclic peptide deformylase inhibitors.

Molteni V, He X, Nabakka J, Yang K, Kreusch A, Gordon P, Bursulaya B, Warner I, Shin T, Biorac T, Ryder NS, Goldberg R, Doughty J, He Y.

Source

Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA. vmolteni@gnf.org

Abstract

Screening of our compound collection using Staphylococcus aureus Ni-Peptide deformylase (PDF) afforded a very potent PDF inhibitor with an IC(50) in the low nanomolar range but with poor antibacterial activity (MIC). Three-dimensional structural information obtained from Pseudomonas aeruginosa Ni-PDF complexed with the inhibitor suggested the synthesis of a variety of analogues that would maintain high binding affinity while attempting to improve antibacterial activity. Many of the compounds synthesized proved to be excellent PDF-Ni inhibitors and some showed increased antibacterial activity in selected strains.

PMID:: 15006385; [PubMed - indexed for MEDLINE]

MeSH Terms, Substances, Secondary Source ID

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Secondary Source ID

PDB/1S17

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Cited by 1 PubMed Central article

Review Challenges of antibacterial discovery. [Clin Microbiol Rev. 2011]
Review Challenges of antibacterial discovery.
Silver LL. Clin Microbiol Rev. 2011 Jan; 24(1):71-109.

Structures reported by this article

Identification Of Novel Potent Bicyclic Peptide Deformylase Inhibitors

PDB: 1S17

Source: Pseudomonas aeruginosa

Method: X-Ray Diffraction

Resolution: 1.95 Å

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