Structure-based design of a macrocyclic inhibitor for peptide deformylase

Xubo Hu¹, Kiet T Nguyen, Christophe L M J Verlinde

¹Department of Chemistry and Ohio State Biochemistry Program, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, USA.

|August 22, 2003

Abstract:

A macrocyclic, peptidomimetic inhibitor of peptide deformylase was designed by covalently cross-linking the P1' and P3' side chains. The macrocycle, which contains an N-formylhydroxylamine side chain as the metal-chelating group, was synthesized from a diene precursor via olefin metathesis using Grubbs's catalyst. The cyclic inhibitor showed potent inhibitory activity toward Escherichia coli deformylase (K(I) = 0.67 nM) and antibacterial activity against both Gram-positive and Gram-negative bacteria (MIC = 0.7-12 microg/mL).

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Abstract:

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