Peptide name : Citropin1.1

Source/Organism : Australian blue mountains tree frog

Linear/Cyclic : Linear

Chirality : L

Peptide length: 16

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information: None

Assay type : MTT/MTS assay

Assay time : 6h

Activity : 60% 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 : 1615.9536 Dalton

Aliphatic index : 1.581

Instability index : 14.1875

Hydrophobicity (GRAVY) : 1.2813

Isoelectric point : 8.5909

Charge (pH 7) : 0.7592

Aromaticity : 0.062

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

Hydrophobic/hydrophilic ratio : 3

hydrophobic moment : -0.312

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

Most occurring amino acid : G

Most occurring amino acid frequency : 3

Least occurring amino acid : F

Least occurring amino acid frequency : 1

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

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

1 : Wegener KL, et al. Host defence peptides from the skin glands of the Australian blue mountains tree-frog Litoria citropa. Solution structure of the antibacterial peptide citropin 1.1. Eur J Biochem. 1999; 265:627-37. doi: 10.1046/j.1432-1327.1999.00750.x

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

Paper title : Host defence peptides from the skin glands of the Australian blue mountains tree-frog Litoria citropa. Solution structure of the antibacterial peptide citropin 1.1.

Doi : https://doi.org/10.1046/j.1432-1327.1999.00750.x

Abstract : Nineteen citropin peptides are present in the secretion from the granular dorsal glands of the Blue Mountains tree-frog Litoria citropa; 15 of these peptides are also present in the secretion from the submental gland. Two major peptides, citropin 1.1 (GLFDVIKKVASVIGGL-NH2), citropin 1.2 (GLFDIIKKVASVVGGL-NH2) and a minor peptide, citropin 1.3 (GLFDIIKKVASVIGGL-NH2) are wide-spectrum antibacterial peptides. The amphibian has an endoprotease which deactivates these membrane-active peptides by removing residues from the N-terminal end: loss of three residues gives the most abundant degradation products. The solution structure of the basic peptide citropin 1.1 has been determined by NMR spectroscopy [in a solvent mixture of trifluoroethanol/water (1 : 1)] to be an amphipathic alpha-helix with well-defined hydrophobic and hydrophilic regions. The additional four peptides produced by the dorsal glands are structurally related to the antibacterial citropin 1 peptides but contain three more residues at their C-terminus [e.g. citropin 1.1.3 (GLFDVIKKVASVIGLASP-OH)]. These peptides show minimal antibacterial activity; their role in the amphibian skin is not known.

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.