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Research Article Free access | 10.1172/JCI115880

Peptides related to the carboxyl terminus of human platelet factor IV with antibacterial activity.

R P Darveau, J Blake, C L Seachord, W L Cosand, M D Cunningham, L Cassiano-Clough, and G Maloney

Immune Science Group, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.

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Immune Science Group, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.

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Immune Science Group, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.

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Immune Science Group, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.

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Immune Science Group, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.

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Immune Science Group, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.

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Immune Science Group, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.

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Published August 1, 1992 - More info

Published in Volume 90, Issue 2 on August 1, 1992
J Clin Invest. 1992;90(2):447–455. https://doi.org/10.1172/JCI115880.
© 1992 The American Society for Clinical Investigation
Published August 1, 1992 - Version history
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Abstract

A peptide (C13) corresponding to the last 13 amino acids of the carboxyl terminus of human platelet factor IV was found to be antibacterial. Amino acid substitutions predicted to disrupt either the amphipathic or alpha-helical nature of C13 rendered the peptide inactive. Antibacterial activity was demonstrated in normal human serum on bacteria which had been previously exposed to low levels of cefepime, a beta-lactam antibiotic. Peptide analogues were examined for more potent antibacterial activity in an antibacterial assay that employed normal human serum and low levels of cefepime. A peptide analogue (C18G) with 80-fold more antibacterial activity than C13 was identified. Studies in C8-deficient sera confirmed an essential role of human serum complement for optimal antibacterial activity. Additional studies showed low levels of cefepime, although not essential, enhanced the antibacterial activity of C18G. Animal protection experiments demonstrated that either peptide C18G or an analogue with all D amino acids (C18X) significantly increased the survival of neutropenic mice when coadministered with a low level of cefepime. This work has resulted in the identification of a new group of antibacterial peptides.

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