Peptide name : Pexiganan MSI-78

Source/Organism : Helical peptide with a predominance of one or more amino acids tryptophane-rich

Linear/Cyclic : Linear

Chirality : L

Peptide length: 22

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information: None

Assay type : MTT/MTS assay

Assay time : 6h

Activity : 75% Cytotoxicity at 0.5 µg/ml

Cell line : U-937

Cancer type : Lymphoma cancer

Other activity : Anti-microbial activity

Amino acid composition bar chart :

Molecular mass : 2478.1585 Dalton

Aliphatic index : 0.931

Instability index : -6.1636

Hydrophobicity (GRAVY) : -0.159

Isoelectric point : 10.903

Charge (pH 7) : 8.7511

Aromaticity : 0.136

Molar extinction coefficient (cysteine, cystine): (0, 0)

Hydrophobic/hydrophilic ratio : 1.44444444

hydrophobic moment : 0.4174

Missing amino acid : C,R,W,H,Q,T,P,M,E,S,D,Y,N

Most occurring amino acid : K

Most occurring amino acid frequency : 9

Least occurring amino acid : V

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.5, 0.1, 0.3)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)CN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O)[C@@H](C)CC)C(C)C

1 : Koszałka P, et al. Antitumor activity of antimicrobial peptides against U937 histiocytic cell line. Acta Biochim Pol. 2011; 58:111-7.

2 : Jacob L and Zasloff M. Potential therapeutic applications of magainins and other antimicrobial agents of animal origin. Ciba Found Symp. 1994; 186:197-216; discussion 216-23. doi: 10.1002/9780470514658.ch12

Paper title : Antitumor activity of antimicrobial peptides against U937 histiocytic cell line.

Doi : https://doi.org/Not available

Abstract : We investigated cytotoxic activity of antimicrobial peptides of different origin (both naturally occurring and synthetic), structure and known mechanisms of action against human histiocytic lymphoma cell line U937. The strongest cytotoxic activity against U937 cell line was shown by Pexiganan MSI-78, followed by Citropin 1.1, Protegrin 1 and a synthetic lipopeptide, N-α-palmitoyl-L-lysyl-L-lysine amide (Pal-Lys-Lys-NH₂). The cytotoxic activity of the peptides was more dependent on the time of incubation than concentration. Only for the lipopeptide, whose mode of action was restricted to disruption of electric potential of the cell membrane, the correlation between cytotoxicity and concentration was almost linear. The high cytotoxicity of Pexiganan MSI-78, Protegrin 1 and the lipopeptide could be basically explained by their membranolytic activity leading to necrosis. However, in the case of Citropin 1.1, the cell membrane integrity was disrupted only slightly and independently of the peptide concentration. Therefore, some other mechanism of action might be responsible for its strong dose-dependent cytotoxic activity, e.g., membranolytic activity leading to apoptosis. Furthermore, TNF-α production due to LPS (lipopolysaccharide) stimulation was suppressed by the presence of Citropin 1.1, Pexiganan MSI-78 or Protegrin 1, but not by Buforin 2 or the lipopeptide. Our experiments have shown that cytotoxic activity is not limited to some specific molecular structure of a peptide, but rather to the length of the peptide chain as it is likely to affect the efficiency of the tumor cell membrane disruption and interaction with LPS.

Paper title : Potential therapeutic applications of magainins and other antimicrobial agents of animal origin.

Doi : https://doi.org/10.1002/9780470514658.ch12

Abstract : Magainins are a family of linear, amphipathic, cationic antimicrobial peptides, 21 to 27 residues in length, found in the skin of Xenopus laevis. They kill microbial targets through disruption of membrane permeability. They exhibit selectivity, on the basis of their affinity for membranes which contain accessible acidic phospholipids, a property characterizing the cytoplasmic membranes of many species of bacteria. Magainins are broad-spectrum antimicrobial agents exhibiting cidal activity against Gram-negative and Gram-positive bacteria, fungi and protozoa. In addition these peptides lyse many types of murine and human cancer cells at concentrations 5-10-fold lower than normal human cells. Because of their selectivity, broad spectrum, low degree of bacterial resistance and ease of chemical synthesis, magainins are being developed as human therapeutic agents. The most advanced candidate is MSI-78, a 22-residue magainin analogue. This peptide is currently in human Phase IIb/III clinical trials in studies intended to evaluate its efficacy as a topical agent for the treatment of impetigo. Preclinical studies have demonstrated that analogues of magainin exhibit activity in vivo against malignant melanoma and ovarian cancer cells in mouse models. Intravenous administration of several magainin analogues has been shown to treat effectively systemic Escherichia coli infections in the mouse.