Synthesis of new antifungal peptides selective against Cryptococcus neoformans

被引：21

作者：

Grimaldi, Manuela ^{[1
]}

De Rosa, Margherita ^{[2
]}

Di Marino, Sara ^{[1
]}

Scrima, Mario ^{[1
]}

Posteraro, Brunella ^{[3
]}

Sanguinetti, Maurizio ^{[3
]}

Fadda, Giovanni ^{[3
]}

Soriente, Annunziata ^{[2
]}

D'Ursi, Anna Maria ^{[1
]}

机构：

[1] Univ Salerno, Dept Pharmaceut Sci, I-84024 Fisciano, SA, Italy

[2] Univ Salerno, Dept Chem, I-84024 Fisciano, SA, Italy

[3] Catholic Univ Sacred Heart L Go F Vito, Inst Microbiol, I-100168 Rome, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 22期

关键词：

Antimicrobial peptides; Cyclo peptide synthesis; Antifungal peptides; ANTIMICROBIAL PEPTIDES; MOLECULAR-DYNAMICS; CANDIDA-ALBICANS; FUNGAL PATHOGENS; DRUG DISCOVERY; CELL-MEMBRANE; TARGET; AGENTS; HEXAPEPTIDES; ANTIBIOTICS;

D O I：

10.1016/j.bmc.2010.09.033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：7985 / 7990

页数：6

共 49 条

[1] Interaction of the antimicrobial peptide cyclo(RRWWRF) with membranes by molecular dynamics simulations [J].