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

稳定的肽抑制剂可防止致死因子和水肿因子与保护性抗原结合并中和体内炭疽毒素

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作者:Alessandro Pini, Ylenia Runci, Chiara Falciani, Barbara Lelli, Jlenia Brunetti, Silvia Pileri, Monica Fabbrini, Luisa Lozzi, Claudia Ricci, Andrea Bernini, Fiorella Tonello, Federica Dal Molin, Paolo Neri, Neri Niccolai, Luisa Bracci

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.

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