Design and synthesis of macrocyclic peptidyl hydroxamates as peptide deformylase inhibitors

Bioorg Med Chem Lett. 2008 May 15;18(10):3060-3. doi: 10.1016/j.bmcl.2007.12.011. Epub 2007 Dec 10.

Abstract

Macrocyclic peptidyl hydroxamates were designed, synthesized, and evaluated as peptide deformylase (PDF) inhibitors. The most potent compound exhibited tight, slow-binding inhibition of Escherichia coli PDF (K(I)(*)=4.4 nM) and had potent antibacterial activity against Gram-positive bacterium Bacillus subtilis (MIC=2-4 microg/mL).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amidohydrolases / antagonists & inhibitors*
  • Amidohydrolases / chemistry
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacillus subtilis / drug effects*
  • Binding, Competitive / drug effects
  • Caproates / chemistry
  • Drug Design*
  • Hydroxamic Acids / chemical synthesis*
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Caproates
  • Hydroxamic Acids
  • Peptides, Cyclic
  • Amidohydrolases
  • peptide deformylase