Small molecule mimics of DFTamP1, a database designed anti-Staphylococcal peptide

Bioorg Med Chem. 2017 Feb 1;25(3):864-869. doi: 10.1016/j.bmc.2016.11.056. Epub 2016 Nov 30.

Abstract

Antimicrobial peptides (AMPs) are important templates for developing new antimicrobial agents. Previously, we developed a database filtering technology that enabled us to design a potent anti-Staphylococcal peptide DFTamP1. Using this same design approach, we now report the discovery of a new class of bis-indole diimidazolines as AMP small molecule mimics. The best compound killed multiple S. aureus clinical strains in both planktonic and biofilm forms. The compound appeared to target bacterial membranes with antimicrobial activity and membrane permeation ability similar to daptomycin.

Keywords: Antimicrobial peptides; Chemical synthesis; Database filtering technology; Peptide mimics.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Molecular Structure
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Peptides
  • Small Molecule Libraries