Peptide name : MK58911 (a peptide Analog from the mastoparan class of wasps)

Source/Organism : Greater wax moth

Linear/Cyclic : Linear

Chirality : L

Peptide length: 14

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information: None

Assay type : Cytotoxicity test

Assay time : 24h

Activity : IC50 : > 500 µg/mL

Cell line : MRC5

Cancer type : Not found

Other activity : Anti-microbial activity; Anti-fungal activity

Amino acid composition bar chart :

Molecular mass : 1642.1036 Dalton

Aliphatic index : 1.392

Instability index : -15.621

Hydrophobicity (GRAVY) : 0.2929

Isoelectric point : 10.477

Charge (pH 7) : 3.7561

Aromaticity : 0.071

Molar extinction coefficient (cysteine, cystine): (5500, 5500)

Hydrophobic/hydrophilic ratio : 1.8

hydrophobic moment : -0.924

Missing amino acid : C,R,H,Q,T,P,E,F,S,D,Y

Most occurring amino acid : K

Most occurring amino acid frequency : 4

Least occurring amino acid : N

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.5, 0.1, 0.4)

SMILES Notation: CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)C)[C@@H](C)CC

1 : Singulani JL, et al. Antifungal Activity, Toxicity, and Membranolytic Action of a Mastoparan Analog Peptide. Front Cell Infect Microbiol. 2019; 9:419. doi: 10.3389/fcimb.2019.00419

Paper title : Antifungal Activity, Toxicity, and Membranolytic Action of a Mastoparan Analog Peptide.

Doi : https://doi.org/10.3389/fcimb.2019.00419

Abstract : Invasive fungal infections, such as cryptococcosis and paracoccidioidomycosis are associated with significant rates of morbidity and mortality. Cryptococcosis, caused by Cryptococcus neoformans, is distributed worldwide and has received much attention as a common complication in patients with HIV. Invasive fungal infections are usually treated with a combination of amphotericin B and azoles. In addition, 5-fluorocytosine (5-FC) is applied in cryptococcosis, specifically to treat central nervous system infection. However, host toxicity, high cost, emerging number of resistant strains, and difficulty in developing new selective antifungals pose challenges. The need for new antifungals has therefore prompted a screen for inhibitory peptides, which have multiple mechanisms of action. The honeycomb moth Galleria mellonella has been widely used as a model system for evaluating efficacy of antifungal agents. In this study, a peptide analog from the mastoparan class of wasps (MK58911) was tested against Cryptococcus spp. and Paracoccidioides spp. In addition, peptide toxicity tests on lung fibroblasts (MRC5) and glioblastoma cells (U87) were performed. Subsequent tests related to drug interaction and mechanism of action were also performed, and efficacy and toxicity of the peptide were evaluated in vivo using the G. mellonella model. Our results reveal promising activity of the peptide, with an MIC in the range of 7.8-31.2 μg/mL, and low toxicity in MRC and U87 cells (IC₅₀ > 500 μg/mL). Taken together, these results demonstrate that MK58911 is highly toxic in fungal cells, but not mammalian cells (SI > 16). The mechanism of toxicity involved disruption of the plasma membrane, leading to death of the fungus mainly by necrosis. In addition, no interaction with the drugs amphotericin B and fluconazole was found either in vitro or in vivo. Finally, the peptide showed no toxic effects on G. mellonella, and significantly enhanced survival rates of larvae infected with C. neoformans. Although not statistically significant, treatment of larvae with all doses of MK58911 showed a similar trend in decreasing the fungal burden of larvae. These effects were independent of any immunomodulatory activity. Overall, these results present a peptide with potential for use as a new antifungal drug to treat systemic mycoses.