Navegando por Palavras-chave "killer peptides"

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    Antibodies as Crypts of Antiinfective and Antitumor Peptides
    (Bentham Science Publ Ltd, 2009-06-01) Magliani, W.; Conti, S.; Cunha, Rodrigo Luiz Oliveira Rodrigues [UNIFESP]; Travassos, Luiz Rodolpho [UNIFESP]; Polonelli, L.; Univ Parma; Universidade Federal de São Paulo (UNIFESP); Dept Microbiol Imunol & Parasitol
    Antibodies (Abs), often associated with antimicrobial and antitumor agents, have emerged as an important class of novel drugs for antigen-driven therapeutic purposes in diverse clinical settings, including oncology and infectious diseases. Abs commonly give rise in the treated host to anti-Ab responses, which may induce adverse reactions and limit their therapeutic efficacy. Their modular domain architecture has been exploited to generate alternative reduced formats (Fabs, scFvs, dAbs, minibodies, multibodies), essentially devoid of the Fc region. The presence of complementarity determining regions (CDRs) ensures the maintenance of selective binding to antigens and supports their use for biotechnological and therapeutic applications. Paradigmatic Abs mimicking the wide-spectrum antimicrobial activity of a yeast killer toxin (killer Abs) have revealed the existence of a family of Abs exerting a direct in vitro and/or in vivo microbicidal activity. Based on the variable sequence of an antiidiotypic recombinant killer Ab, CDR-related peptides have been synthesized, engineered by alanine-scanning and selected according to antimicrobial, antiviral and immunomodulatory properties. Irrespective of the native Ab specificity, synthetic CDRs from unrelated murine and human monoclonal Abs, have shown to display differential in vitro, in vivo and/or ex vivo antifungal (Candida albicans), antiviral (HIV-1) and antitumor (melanoma cells) activities. Alanine substitution of single residues of synthetic CDR peptides resulted in further differential increased/unaltered/decreased biological activity. The intriguing potential of Abs as source of antiinfective and antitumor therapeutics will be discussed, in light of recent advances in peptide design, stability and delivery.
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    From yeast killer toxins to antibiobodies and beyond
    (Wiley-Blackwell, 2008-11-01) Magliani, Walter; Conti, Stefania; Travassos, Luiz R. [UNIFESP]; Polonelli, Luciano; Univ Parma; Universidade Federal de São Paulo (UNIFESP)
    Antibiobodies are paradigmatic of yeast killer toxin (KT)-like antibodies (KAbs) mimicking the antimicrobial activity of KTs in the frame of the yeast killer phenomenon. Polyclonal, monoclonal and recombinant anti-idiotypic antibiobodies (anti-idiotypic KAbs), internal images of a wide-spectrum KT produced by the yeast Pichia anomala (PaKT), have been produced by immunization with the idiotype of a PaKT-neutralizing monoclonal antibody. Anti-idiotypic KAbs showed microbicidal activity against eukaryotic and prokaryotic pathogenic agents through the interaction with specific KT receptors (KTRs), putatively constituted by beta-glucans. Natural KAbs have been found in animals and humans experimentally or naturally infected by KTR-bearing microorganisms. Recombinant KAb-derived synthetic killer peptides showed further antiviral and immunomodulatory activities. the perspectives of KAbs and killer peptides as potential sources of novel therapeutic agents, and of KTRs and idiotypes as vaccines against infectious diseases are discussed.