Peptide name : Tritrp-W678Y

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 13

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : MTT assay

Assay time : 24-h

Activity : IC50 ≥ 65 μM

Cell line : Jurkat

Cancer type : Blood Cancer

Other activity : Antimicrobial

Amino acid composition bar chart :

Molecular mass : 1833.1443 Dalton

Aliphatic index : 0.523

Instability index : 170.276

Hydrophobicity (GRAVY) : -0.884

Isoelectric point : 10.931

Charge (pH 7) : 3.731

Aromaticity : 38.46

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

Hydrophobic/hydrophilic ratio : 0.8571

hydrophobic moment : 0.4163

Missing amino acid : A,C,D,E,G,H,I,K,M,N,Q,S,T,W

Most occurring amino acid : R

Most occurring amino acid frequency : 4

Least occurring amino acid : V

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (7.6, 15., 53.)

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O

1 : Arias M, et al. Selective anticancer activity of synthetic peptides derived from the host defence peptide tritrpticin. Biochim Biophys Acta Biomembr. 2020; 1862:183228. doi: 10.1016/j.bbamem.2020.183228

Paper title : Selective anticancer activity of synthetic peptides derived from the host defence peptide tritrpticin.

Doi : https://doi.org/10.1016/j.bbamem.2020.183228

Abstract : Antimicrobial peptides (AMPs) constitute a diverse family of peptides with the ability to protect their host against microbial infections. In addition to their ability to kill microorganisms, several AMPs also exhibit selective cytotoxicity towards cancer cells and are collectively referred to as anticancer peptides (ACPs). Here a large library of AMPs, mainly derived from the porcine cathelicidin peptide, tritrpticin (VRRFPWWWPFLRR), were assessed for their anticancer activity against the Jurkat T cell leukemia line. These anticancer potencies were compared to the cytotoxicity of the peptides towards normal cells isolated from healthy donors, namely peripheral blood mononuclear cells (PBMCs) and red blood cells (RBCs; where hemolytic activity was assessed). Among the active tritrpticin derivatives, substitution of Arg by Lys enhanced the selectivity of the peptides towards Jurkat cells when compared to PBMCs. Additionally, the side chain length of the Lys residues was also optimized to further enhance the tritrpticin ACP selectivity at low concentrations. The mechanism of action of the peptides with high selectivity involved the permeabilization of the cytoplasmic membrane of Jurkat cells, without formation of apoptotic bodies. The incorporation of non-natural Lys-based cationic amino acids could provide a new strategy to improve the selectivity of other synthetic ACPs to enhance their potential for therapeutic use against leukemia cells.