Peptide deformylase inhibitors of Mycobacterium tuberculosis: synthesis, structural investigations, and biological results.

Article Details

Citation

Copy to clipboard

Pichota A, Duraiswamy J, Yin Z, Keller TH, Alam J, Liung S, Lee G, Ding M, Wang G, Chan WL, Schreiber M, Ma I, Beer D, Ngew X, Mukherjee K, Nanjundappa M, Teo JW, Thayalan P, Yap A, Dick T, Meng W, Xu M, Koehn J, Pan SH, Clark K, Xie X, Shoen C, Cynamon M

Peptide deformylase inhibitors of Mycobacterium tuberculosis: synthesis, structural investigations, and biological results.

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6568-72. doi: 10.1016/j.bmcl.2008.10.040. Epub 2008 Oct 14.

PubMed ID

19008098 [ View in PubMed

]

Abstract

Bacterial peptide deformylase (PDF) belongs to a subfamily of metalloproteases catalyzing the removal of the N-terminal formyl group from newly synthesized proteins. We report the synthesis and biological activity of highly potent inhibitors of Mycobacterium tuberculosis (Mtb) PDF enzyme as well as the first X-ray crystal structure of Mtb PDF. Structure-activity relationship and crystallographic data clarified the structural requirements for high enzyme potency and cell based potency. Activities against single and multi-drug-resistant Mtb strains are also reported.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
N-[(2R)-2-{[(2S)-2-(1,3-benzoxazol-2-yl)pyrrolidin-1-yl]carbonyl}hexyl]-N-hydroxyformamide	Peptide deformylase	IC 50 (nM)	13	N/A	N/A	Details