Effective Antimicrobial and Anti-Endotoxin Activity of Cationic Peptides Based on Lactoferricin: A Biophysical and Microbiological Study

ISSN: 2211-3533 (Online)
ISSN: 2211-3525 (Print)

Volume 14, 2 Issues, 2016

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Anti-Infective Agents

Formerly: Anti-Infective Agents in Medicinal Chemistry

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Effective Antimicrobial and Anti-Endotoxin Activity of Cationic Peptides Based on Lactoferricin: A Biophysical and Microbiological Study

Anti-Infective Agents, 9(1): 9-22.

Author(s): Klaus Brandenburg, Jorg Howe, Susana Sanchez-Gomez, Patrick Garidel, Manfred Roessle, Jorg Andra, Roman Jerala, Dagmar Zweytick, Karl Lohner, Michael Rappolt, Sylvie Blondelle, Ignacio Moriyon and Guillermo Martinez de Tejada.

Affiliation: Forschungszentrum Borstel,Leibniz-Zentrum fur Medizin und Biowissenschaften, Biophysik, Parkallee 10, 23845 Borstel, Germany.


Bacterial endotoxins (lipopolysaccharide, LPS) from the outer leaflet of the outer membrane of Gram-negative bacteria are among the most effective natural compounds in triggering the human innate immune system. This may be beneficial at low but pathophysiological at high LPS concentrations, the latter leading to the severe septic shock syndrome with still high mortality rates especially in intensity care units.

One approach to inactivate compounds such as LPS is the use of cationic amphiphilic peptides based on natural endotoxin- binding proteins, which are designed to neutralize bacterial LPS and thus inhibit its interaction with relevant mammalian binding proteins/ receptors such as lipopolysaccharide-binding protein (LBP), CD14, and TLR4/MD2. We have designed and synthesized peptides based on human lactoferricin, and have applied in an iterative process (first to third generation) various experimental systems to test their ability to fight against bacterial sepsis. Here, four compounds from the third generation were selected, with and without a short hydrocarbon chain, and analysed in detail starting from biophysical over cell biological and microbiological assays up to animal experiments. Thus, we were able to characterize the parameters relevant in endotoxin deactivation, as part of the bacterial cell as well as in isolated form. The most important parameters include the peptide length, number of cationic amino acids, and hydrophobicity of the peptides.


Sepsis, lipopolysaccharide, small-angle X-ray scattering, lactoferricin, antimicrobial peptides.

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Article Details

Volume: 9
Issue Number: 1
First Page: 9
Last Page: 22
Page Count: 14
DOI: 10.2174/187152110790886736
Superbugs USA

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