title: Dissecting the Structure-Function Relationship of a Fungicidal Peptide Derived from the Constant Region of Human Immunoglobulins.
abstract: 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 activitiesin vitroand/orin vivo, regardless of the specificity and isotype of the parental antibody. Alanine substitution derivatives of these peptides exhibited unaltered, increased, or decreased candidacidal activitiesin 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 withCandida albicanscells 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 aGalleria mellonellamodel. 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 peptidesin vitroand their therapeutic effectsin vivo.
authors: Unit of Microbiology and Virology, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
authors: Tecla
authors: T
authors: Ciociola
authors: CIM Laboratory, Technopole Parma, University of Parma, Parma, Italy.
authors: Thelma A
authors: TA
authors: Pertinhez
authors: Unit of Microbiology and Virology, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
authors: Laura
authors: L
authors: Giovati
authors: Unit of Microbiology and Virology, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
authors: Martina
authors: M
authors: Sperindè
authors: Unit of Microbiology and Virology, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
authors: Walter
authors: W
authors: Magliani
authors: Unit of Biochemistry, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
authors: Elena
authors: E
authors: Ferrari
authors: Unit of Anatomy, Histology and Embryology, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
authors: Rita
authors: R
authors: Gatti
authors: Unit of Pathologic Anatomy, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
authors: Tiziana
authors: T
authors: D'Adda
authors: Department of Surgical Sciences, University of Parma, Parma, Italy.
authors: Alberto
authors: A
authors: Spisni
authors: Unit of Microbiology and Virology, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy stefania.conti@unipr.it.
authors: Stefania
authors: http://orcid.org/0000-0001-9973-8352
authors: S
authors: Conti
authors: Unit of Microbiology and Virology, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
authors: Luciano
authors: L
authors: Polonelli
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009036:Moths / Q000187:drug effects / Q000382:microbiology; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000032:analysis / Q000378:metabolism; D013329:Structure-Activity Relationship; D016019:Survival Analysis
chemical_list: D000935:Antifungal Agents; D022801:Complementarity Determining Regions; D007074:Immunoglobulin G; D010455:Peptides; D010718:Phosphatidylserines