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 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.
| Original language | English |
|---|---|
| Pages (from-to) | 2435-2442 |
| Number of pages | 8 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 60 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2016 |
Fingerprint
ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology
- Infectious Diseases
Cite this
Dissecting the structure-function relationship of a fungicidal peptide derived from the constant region of human immunoglobulins. / Ciociola, Tecla; Pertinhez, Thelma A.; Giovati, Laura; Sperindè, Martina; Magliani, Walter; Ferrari, Elena; Gatti, Rita; D'Adda, Tiziana; Spisni, Alberto; Conti, Stefania; Polonelli, Usciano.
In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 4, 01.04.2016, p. 2435-2442.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dissecting the structure-function relationship of a fungicidal peptide derived from the constant region of human immunoglobulins
AU - Ciociola, Tecla
AU - Pertinhez, Thelma A.
AU - Giovati, Laura
AU - Sperindè, Martina
AU - Magliani, Walter
AU - Ferrari, Elena
AU - Gatti, Rita
AU - D'Adda, Tiziana
AU - Spisni, Alberto
AU - Conti, Stefania
AU - Polonelli, Usciano
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84963690695&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963690695&partnerID=8YFLogxK
U2 - 10.1128/AAC.01753-15
DO - 10.1128/AAC.01753-15
M3 - Article
AN - SCOPUS:84963690695
VL - 60
SP - 2435
EP - 2442
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 4
ER -