title: Stable peptide inhibitors prevent binding of lethal and oedema factors to protective antigen and neutralize anthrax toxin in vivo.
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.
authors.affiliation: Department of Molecular Biology, University of Siena, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pini
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Runci
authors.forename: Chiara
authors.initials: C
authors.lastname: Falciani
authors.forename: Barbara
authors.initials: B
authors.lastname: Lelli
authors.forename: Jlenia
authors.initials: J
authors.lastname: Brunetti
authors.forename: Silvia
authors.initials: S
authors.lastname: Pileri
authors.forename: Monica
authors.initials: M
authors.lastname: Fabbrini
authors.forename: Luisa
authors.initials: L
authors.lastname: Lozzi
authors.forename: Claudia
authors.initials: C
authors.lastname: Ricci
authors.forename: Andrea
authors.initials: A
authors.lastname: Bernini
authors.forename: Fiorella
authors.initials: F
authors.lastname: Tonello
authors.forename: Federica
authors.initials: F
authors.lastname: Dal Molin
authors.forename: Paolo
authors.initials: P
authors.lastname: Neri
authors.forename: Neri
authors.initials: N
authors.lastname: Niccolai
authors.forename: Luisa
authors.initials: L
authors.lastname: Bracci
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000096:biosynthesis; D019151:Peptide Library; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D014757:Viper Venoms / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; D014757:Viper Venoms; C030325:anthrax toxin; C416405:edema factor; D000242:Cyclic AMP