PMID: 11906603Mar 22, 2002Paper

Peptides with indirect in vivo activity against an intracellular pathogen: selective lysis of infected macrophages

The Journal of Peptide Research : Official Journal of the American Peptide Society
T S YokumP H Elzer

Abstract

A collection of natural peptides, simplified analogs of natural peptides, de novo amphipathic peptides and de novo amphipathic peptides composed of 50-80% alpha,alpha-dialkylated glycines (alpha,alpha-Dags) were synthesized on solid-phase resin as the C-terminus amides using N-alpha-fluorenylmethyloxycarbonyl protection. The synthesis of the peptides rich in alpha,alpha-Dags used acid fluoride coupling methods. The peptides show antimicrobial activity against Escherichia coli and Staphylococcus aureus but no direct antimicrobial activity against Brucella abortus at 100 microm in vitro. However, in vivo treatment with several of these peptides results in significant reductions of B. abortus in chronically infected immune BALB/c mice relative to infected control animals. The chronically infected mice were susceptible to peptide toxicity at much lower peptide doses than control animals. The highest nonlethal dose for infected mice was only 25 microg for melittin, whereas 500 microg doses were nonlethal for many of the other peptides. Several of the alpha,alpha-Dag-rich peptides selectively destroy B. abortus-infected murine macrophages in vitro. Thus, these peptides apparently reduce the bacterial load in vivo by destroying a port...Continue Reading

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Citations

Jun 1, 2012·Expert Opinion on Drug Discovery·Karine Estieu-Gionnet, Gilles Guichard
May 1, 2015·Antibiotics·Victor I Band, David S Weiss
Dec 1, 2005·The Journal of Peptide Research : Official Journal of the American Peptide Society·S R HaynesR P Hammer
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sherri DudalVirginie Lafont

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