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Simple oligomers as antimicrobial peptide mimics

  • Jason Rennie
  • Lachelle Arnt
  • Haizhong Tang
  • Klaus NüssleinEmail author
  • Gregory N. Tew
Special Topic: Disinfectants and Microbial Control

Abstract

New approaches to antibiotic design are desperately needed. The design of simple oligomers that capture the shape and biological function of natural antimicrobial peptides could prove to be versatile and highly successful. We discuss the use of aromatic backbones to design facially amphiphilic (FA) β-sheet like structures which are potently antimicrobial. These oligomers capture the physiochemical properties of peptides like the Magainins and Defensins, which fold into specific conformations that are amphiphilic resulting in antimicrobial activity. However, natural peptides are expensive to prepare and difficult to produce on large scale. The design of polymers and oligomers that mimic the complex structures and remarkable biological properties of proteins is an important endeavor and provides attractive alternatives to the difficult synthesis of natural peptides. We therefore have designed a series of FA oligomers that are easy to prepare from inexpensive monomers. They adopt structures very reminiscent of amphiphilic β-sheets and have significant activity with minimal inhibitory concentrations at 6 h in the low microgram per ml range (μM to nM). They are active against a broad spectrum of bacteria including gram-positive and gram-negative as well as antibiotic resistant strains.

Keywords

Magainin Host defense peptides Phenylene ethynylene Facially amphiphilic Antibacterial 

Notes

Acknowledgements

This work was supported in part by the National Science Foundation Biocomplexity Program (CHE-0221791) to K.N., the National Institutes of Health (GM-065803) and ONR Young Investigator (N00014-03-1-0503) to G.N.T. G.N.T gratefully acknowledges the PECASE program, ARO for a Young Investigator Award, 3M Nontenured Faculty Award, and DuPont Young Faculty Grant.

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Copyright information

© Society for Industrial Microbiology 2005

Authors and Affiliations

  • Jason Rennie
    • 1
  • Lachelle Arnt
    • 2
  • Haizhong Tang
    • 2
  • Klaus Nüsslein
    • 1
    Email author
  • Gregory N. Tew
    • 2
  1. 1.Department of MicrobiologyUniversity of MassachusettsAmherstUSA
  2. 2. Polymer Science and Engineering DepartmentUniversity of MassachusettsAmherstUSA

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