Stable peptide inhibitors prevent binding of lethal and oedema factors to protective antigen and neutralize anthrax toxin in vivo

Author:

Pini Alessandro1,Runci Ylenia1,Falciani Chiara1,Lelli Barbara1,Brunetti Jlenia1,Pileri Silvia1,Fabbrini Monica1,Lozzi Luisa1,Ricci Claudia1,Bernini Andrea1,Tonello Fiorella2,Dal Molin Federica3,Neri Paolo1,Niccolai Neri1,Bracci Luisa1

Affiliation:

1. Department of Molecular Biology, University of Siena, Via Fiorentina 1, 53100 Siena, Italy

2. Neuroscience Institute, CNR, 35121 Padova, Italy

3. Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy

Abstract

The lethal and oedema toxins produced by Bacillus anthracis, the aetiological agent of anthrax, are made by association of protective antigen with lethal and oedema factors and play a major role in the pathogenesis of anthrax. In the present paper, we describe the production of peptide-based specific inhibitors in branched form which inhibit the interaction of protective antigen with lethal and oedema factors and neutralize anthrax toxins in vitro and in vivo. Anti-protective antigen peptides were selected from a phage library by competitive panning with lethal factor. Selected 12-mer peptides were synthesized in tetra-branched form and were systematically modified to obtain peptides with higher affinity and inhibitory efficiency.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

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