Simple oligomers as antimicrobial peptide mimics

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) beta-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 beta-sheets and have significant activity with minimal inhibitory concentrations at 6 h in the low microgram per ml range (muM to nM). They are active against a broad spectrum of bacteria including gram-positive and gram-negative as well as antibiotic resistant strains.

Infectious disease: Connecting innate immunity to biocidal polymers

“…In this test, treated polymer was shaped into plates and polymer surfaces were held in contact with bacterial cell suspension (10 6 CFU/mL) using sterile cover and kept for 24 h in humid conditions at 37 °C. The number of viable cells was counted after plating on agar and expressed in colony forming units per milliliter (CFU/mL) Tew and coworkers tested the activity of AMMs incorporated in PU coatings by spraying the samples with E. coli followed by immersion in bacterial growth media for 72 h [67]. Microscopy showed that the untreated sample (left) is significantly colonized while the treated sample (right) does not support E. coli growth (Fig 18).…”

“…Tew and coworkers incorporated AMMs into polyurethane (PU) coatings which showed excellent inhibition of E.coli growth on the surface despite immersion in rich growth media for 72 h [67]. More recently, AMM blended into medical grade catheter tubing prevented S. aureus growth completely even after repeated exposure.…”

“…The section on biophysical techniques will elaborate more on these studies. Lastly, imaging of polymer-treated polyurethane samples showed strong prevention of bacteria growth on the surface in preliminary materials studies [67].…”

Activity of an Antimicrobial Peptide Mimetic against Planktonic and Biofilm Cultures of Oral Pathogens

“…The quest for new and improved antimicrobial peptides has led to the study of peptide mimetics (30). Investigators in this field have developed a series of inexpensive nonpeptidic oligomers and polymers, modeled after compounds found in nature, that adopt amphiphilic secondary structures and exhibit potent and selective antimicrobial activity (25). Modifications of these molecules have resulted in the identification of small-molecule oligomers that have molecular masses ranging from 690 to 1,000 Da, that potently inhibit the growth of both gram-negative and gram-positive bacteria, and that exhibit low hemolytic activity (29).…”

Dark Antimicrobial Mechanisms of Cationic Phenylene Ethynylene Polymers and Oligomers against Escherichia coli

“…MIC values were determined by a modified method from literature [24,25]. The E. coli cells were diluted with a minimal medium (28 mM glucose, 42 mM Na 2 HPO 4 , 22 mM KH 2 PO 4 , 18.7 mM NH 4 Cl, 8.5 mM NaCl, 1 mM MgSO 4 , and 0.09 mM CaCl 2 at pH 7.2.…”