The synthetic peptide T11F (TCRVDHRGLTF), derived from the constant region of human IgM antibodies, proved to exert a significant activity in vitro against yeast strains, including multidrug resistant isolates. Alanine substitution of positively charged residues led to a decrease in candidacidal activity. A more dramatic reduction in activity resulted from cysteine replacement. Here, we investigated the conformational properties of T11F and its alanine-substituted derivatives by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. Peptide interaction with Candida albicans cells was studied by confocal and scanning electron microscopy. T11F and most of its derivatives exhibited CD spectra with a negative band around 200 nm and a weaker positive band around 218 nm suggesting, together with NMR coupling constants, the presence of a polyproline II (PPII) helix, a conformational motif involved in a number of biological functions. Analysis of CD spectra revealed a critical role for phenylalanine in preserving the PPII helix. In fact, only the F11A derivative presented a random coil conformation. Interestingly, the loss of secondary structure influenced the rate of killing, which turned out to be significantly reduced. Overall, the obtained results suggest that the PPII conformation contributes in characterising the cell penetrating and fungicidal properties of the investigated peptides.

Dissection of the Structural Features of a Fungicidal Antibody-Derived Peptide / Pertinhez, Thelma A.; Ciociola, Tecla; Giovati, Laura; Magliani, Walter; Belletti, Silvana; Polonelli, Luciano; Conti, Stefania; Spisni, Alberto. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 19:12(2018), p. 3792. [10.3390/ijms19123792]

Dissection of the Structural Features of a Fungicidal Antibody-Derived Peptide

Pertinhez, Thelma A.;Ciociola, Tecla;Giovati, Laura;Magliani, Walter;Belletti, Silvana;Polonelli, Luciano;Conti, Stefania;Spisni, Alberto
2018

Abstract

The synthetic peptide T11F (TCRVDHRGLTF), derived from the constant region of human IgM antibodies, proved to exert a significant activity in vitro against yeast strains, including multidrug resistant isolates. Alanine substitution of positively charged residues led to a decrease in candidacidal activity. A more dramatic reduction in activity resulted from cysteine replacement. Here, we investigated the conformational properties of T11F and its alanine-substituted derivatives by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. Peptide interaction with Candida albicans cells was studied by confocal and scanning electron microscopy. T11F and most of its derivatives exhibited CD spectra with a negative band around 200 nm and a weaker positive band around 218 nm suggesting, together with NMR coupling constants, the presence of a polyproline II (PPII) helix, a conformational motif involved in a number of biological functions. Analysis of CD spectra revealed a critical role for phenylalanine in preserving the PPII helix. In fact, only the F11A derivative presented a random coil conformation. Interestingly, the loss of secondary structure influenced the rate of killing, which turned out to be significantly reduced. Overall, the obtained results suggest that the PPII conformation contributes in characterising the cell penetrating and fungicidal properties of the investigated peptides.
Dissection of the Structural Features of a Fungicidal Antibody-Derived Peptide / Pertinhez, Thelma A.; Ciociola, Tecla; Giovati, Laura; Magliani, Walter; Belletti, Silvana; Polonelli, Luciano; Conti, Stefania; Spisni, Alberto. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 19:12(2018), p. 3792. [10.3390/ijms19123792]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2853623
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