Abstract
Peptides are remarkably reactive molecules produced by a great variety of species and able to display a number of functions in uni-and multicellular organisms as mediators, agonists and regulating substances. Some of them exert cytotoxic effects on cells other than those that produced them, and may have a role in controlling subpopulations and protecting certain species or cell types. Presently, we focus on antifungal and antitumor peptides and discuss a few models in which specific sequences and structures exerted direct inhibitory effects or stimulated a protective immune response. The killer peptide, deduced from an antiidiotypic antibody, with several antimicrobial activities and other Ig-derived peptides with cytotoxic activities including antitumor effects, are models studied in vitro and in vivo. Peptide 10 from gp43 of P. brasiliensis (P10) and the vaccine perspective against paracoccidioidomycosis is another topic illustrating the protective effect in vivo against a pathogenic fungus. The cationic antimicrobial peptides with antitumor activities are mostly reviewed here. Local treatment of murine melanoma by the peptide gomesin is another model studied at the Experimental Oncology Unit of UNIFESP.
Highlights
Bioactive peptides arise from proteins by the action of peptidases or are chemically synthesized based on certain templates of natural sequences that have been selected by a variety of screening methods
Killer antibodies with the internal image of the active site of a killer toxin, which acted as antibiotics, were obtained
In a dividing cell with a big vacuole and chromatin condensation and fragmentation, cellular alterations were seen beyond the septum separating both cells, with the daughter cell already affected by the killer peptide (KP) showing an altered cell wall (Fig. 1B)
Summary
Bioactive peptides arise from proteins by the action of peptidases or are chemically synthesized based on certain templates of natural sequences that have been selected by a variety of screening methods. Magainins are antifungal peptides produced by the African frog Xenopus laevis (De Lucca and Walsh 2000) They are not hemolytic and inhibit Candida albicans (Zasloff 1987). Killer yeasts secrete killer toxins that target susceptible cells in a two-step receptor-mediated manner They bind to cell wall receptors and translocate to the plasma membrane. Killer toxins can induce apoptosis mediated by yeast caspase Yca1p, characterized by DNA fragmentation, and phosphatidylserine external membrane expression This could be a general cell death mechanism under natural environmental conditions (Paluszynski et al 2007, Schmitt and Reiter 2008). Killer antibodies with the internal image of the active site of a killer toxin, which acted as antibiotics, were obtained They exerted significant therapeutic effects in experimental models of candidiasis, aspergillosis and pneumocystosis. In a dividing cell with a big vacuole and chromatin condensation and fragmentation, cellular alterations were seen beyond the septum separating both cells, with the daughter cell already affected by the KP showing an altered cell wall (Fig. 1B)
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