Pichota, Arkadius, Duraiswamy, Jeyaraj, Yin, Zheng, Keller, Thomas, Alam, Jenefer, Liung, Sarah, Lee, Gladys, Ding, Mei, Wang, Gang, Chan, Wai Ling, Schreiber, Mark, Ma, Ida, Beer, David, Ngew, Xinyi, Mukherjee, Kakoli, Nanjundappa, Mahesh, Teo, Jeanette, Thayalan, Pamela, Yap, Amelia, Dick, Thomas, Meng, Wuyi, Xu, Mei, Koehn, James, Pan, Shihao, Clark, Kirk, Xie, Xiaoling, Shoen, Carolyn and Cynamon, Michael (2008) Peptide deformylase inhibitors of Mycobacterium tuberculosis: synthesis, structural investigations, and biological results. Bioorganic & Medicinal Chemistry Letters, 18 (24). pp. 6568-6572. ISSN 0960-894X

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.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2008.10.040
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2008.10.040
Date Deposited:	14 Dec 2009 14:02
Last Modified:	31 Jan 2013 01:23
URI:	https://oak.novartis.com/id/eprint/233