Journal article

Advantage of a Narrow Spectrum Host Defense (Antimicrobial) Peptide Over a Broad Spectrum Analog in Preclinical Drug Development

Eszter Ostorhazi, Ralf Hoffmann, Nicole Herth, John D Wade, Carl N Kraus, Laszlo Otvos

FRONTIERS IN CHEMISTRY | FRONTIERS MEDIA SA | Published : 2018

Abstract

The APO-type proline-arginine-rich host defense peptides exhibit potent in vitro killing parameters against Enterobacteriaceae but not to other bacteria. Because of the excellent in vivo properties against systemic and local infections, attempts are regularly made to further improve the activity spectrum. A C-terminal hydrazide analog of the Chex1-Arg20 amide (ARV-1502) shows somewhat improved minimal inhibitory concentration against Moraxellaceae. Here we compared the activity of the two peptides as well as an inactive dimeric reverse amide analog in a systemic Acinetobacter baumannii infection. Only the narrow spectrum amide derivative reduced the 6-h blood bacterial burden by >2 log10 uni..

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Grants

Awarded by National Institutes of Health


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

This work was partially supported from grant R42 AI136065 from the National Institutes of Health. JW is an NHMRC (Australia) Principal Research Fellow (APP1117483). Research at the Florey Institute of Neuroscience and Mental Health is supported by the Victorian Government Operational Infrastructure Support Program.