Antifungal and antitumor models of bioactive protective peptides

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.

From antimicrobial to anticancer peptides. A review

“…This entrance might lead to the disruption of the cell membrane accompanied by pore formation and/or changes on the cell membrane charge (Janek et al, 2013) and finally the interference with necrotic (Maher and McClean, 2008; Huang et al, 2011; Ausbacher et al, 2012; Wang et al, 2013a) and apoptotic pathways (Ausbacher et al, 2012). Pore formation is a mechanism associated to some AMPs and has been reported for ACPs as well (Rodrigues et al, 2009). The insertion of bulky hydrophobic amino acids on the cell membrane hydrophobic core with the acquisition of a stable structure can be the driving events for pore formation (Hilchie et al, 2011).…”

“…In a structural point of view, most ACPs have either α-helical or β-sheet conformation but some extended structures have already been reported (Hoskin and Ramamoorthy, 2008; Rodrigues et al, 2009; Wang et al, 2009a; Hammami and Fliss, 2010). Concerning cell targets, they can be classified into two major groups.…”

Identification and characterization of a bactericidal and proapoptotic peptide from cycas revoluta seeds with DNA binding properties

“…The 3D non‐acetylated anticancer peptide model presented cationic (Lys 3 ) and aromatic (Trp 2 ) residues forming a single amphipathic α‐helice that showed 55% of hydrophobic residues. This structural fold is commonly found in peptides with multiple activities such as antimicrobial, antifungal, and antitumoral [Rodrigues et al, 2009]. Helene and Maurizot [Helene and Maurizot, 1981] have observed that short oligopeptides containing basic and aromatic residues provided simple systems where it was possible to differentiate between single‐stranded and double‐stranded structures by inserting their aromatic residue between successive bases.…”

On the selectivity and efficacy of defense peptides with respect to cancer cells

“…The primary function of defense peptides is to serve as naturally occurring antibiotics of the innate immune system, targeting a wide variety of microbes ranging from bacteria and viruses to parasites and fungi . However, over the last decade, it has become increasingly clear that many of these peptides also possess a potent ability to inactivate a wide range of cancer cells . A number of articles and databases have listed these anticancer peptides (ACPs), and inspection of these sources shows that the vast majority of ACPs are cationic and adopt molecular architecture that is either β‐sheet (β‐ACPs) or α‐helical (α‐ACPs), although several extended ACPs (E‐ACPs) have been described (Tables and ) .…”