Synthetic peptides encompassing sequences related to the complementarity-determining regions of antibodies or derived from their constant region (Fc peptides) were proven to exert differential antimicrobial, antiviral, antitumor, and/or immunomodulatory activities in vitro and/or in vivo, regardless of the specificity and isotype of the parental antibody. Alanine substitution derivatives of these peptides exhibited unaltered, increased, or decreased candidacidal activities in vitro. The bioactive IgG-derived Fc N10K peptide (NQVSLTCLVK) spontaneously self-assembles, a feature previously recognized as relevant for the therapeutic activity of another antibody-derived peptide. We evaluated the contribution of each residue to the peptide self-assembling capability by circular-dichroism spectroscopy. The interaction of the N10K peptide and its derivatives with Candida albicans cells was studied by confocal, transmission, and scanning electron microscopy. The apoptosis and autophagy induction profiles in yeast cells treated with the peptides were evaluated by flow cytometry, and the therapeutic efficacy against candidal infection was studied in a Galleria mellonella model. Overall, the results indicate a critical role for some residues in the self-assembly process and a correlation of that capability with the candidacidal activities of the peptides in vitro and their therapeutic effects in vivo.
Dissecting the structure-function relationship of a fungicidal peptide derived from the constant region of human immunoglobulins / Ciociola, T.; Pertinhez, T.; Giovati, L.; Sperindè, M.; Magliani, W.; Ferrari, E.; Gatti, R.; D'Adda, T.; Spisni, A.; Conti, S.; Polonelli, L.. - In: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. - ISSN 1098-6596. - 60:4(2016), pp. 2435-2442. [10.1128/AAC.01753-15]
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