TY - JOUR
T1 - Synthesis of new antifungal peptides selective against Cryptococcus neoformans
AU - Grimaldi, Manuela
AU - De Rosa, Margherita
AU - Di Marino, Sara
AU - Scrima, Mario
AU - Posteraro, Brunella
AU - Sanguinetti, Maurizio
AU - Fadda, Giovanni
AU - Soriente, Annunziata
AU - D'Ursi, Anna Maria
PY - 2010
Y1 - 2010
N2 - Many drugs are available for the treatment of systemic or superficial mycoses, but only a limited number of them are effective antifungal drugs, devoid of toxic and undesirable side effects. Furthermore, resistance development and fungistatic rather than fungicidal activities represent limitations of current antifungal therapy. Therefore there remains an urgent need for a new generation of antifungal agents. According to a polypharmacological approach, the present work concerns the synthesis and antifungal activity of a set of peptides designed to simultaneously target the fungal cell surface and lanosterol demethylase, a key enzyme involved in ergosterol synthesis. Our peptides include amino acid sequences characteristic of membrane-active antimicrobial peptides (AMP), and due to the presence of His residues, they carry the imidazole ring characteristic of azole compounds. The peptides synthesized by us, were tested against different yeast species, and displayed general antifungal activity, with a therapeutically promising antifungal specificity against Cryptococcus neoformans.
AB - Many drugs are available for the treatment of systemic or superficial mycoses, but only a limited number of them are effective antifungal drugs, devoid of toxic and undesirable side effects. Furthermore, resistance development and fungistatic rather than fungicidal activities represent limitations of current antifungal therapy. Therefore there remains an urgent need for a new generation of antifungal agents. According to a polypharmacological approach, the present work concerns the synthesis and antifungal activity of a set of peptides designed to simultaneously target the fungal cell surface and lanosterol demethylase, a key enzyme involved in ergosterol synthesis. Our peptides include amino acid sequences characteristic of membrane-active antimicrobial peptides (AMP), and due to the presence of His residues, they carry the imidazole ring characteristic of azole compounds. The peptides synthesized by us, were tested against different yeast species, and displayed general antifungal activity, with a therapeutically promising antifungal specificity against Cryptococcus neoformans.
KW - Amino Acid Sequence
KW - Antifungal Agents
KW - Antimicrobial Cationic Peptides
KW - Circular Dichroism
KW - Cryptococcus neoformans
KW - Enzyme Inhibitors
KW - Fungal Proteins
KW - Microbial Sensitivity Tests
KW - Protein Structure, Secondary
KW - Amino Acid Sequence
KW - Antifungal Agents
KW - Antimicrobial Cationic Peptides
KW - Circular Dichroism
KW - Cryptococcus neoformans
KW - Enzyme Inhibitors
KW - Fungal Proteins
KW - Microbial Sensitivity Tests
KW - Protein Structure, Secondary
UR - http://hdl.handle.net/10807/17416
U2 - 10.1016/j.bmc.2010.09.033
DO - 10.1016/j.bmc.2010.09.033
M3 - Article
SN - 1464-3391
VL - 18
SP - 7985
EP - 7990
JO - BIOORGANIC & MEDICINAL CHEMISTRY
JF - BIOORGANIC & MEDICINAL CHEMISTRY
ER -