Peptide name : Brevinin-2R

Source/Organism : Skin, Marsh frog, Europe

Linear/Cyclic : Not found

Chirality : Not found

Peptide length: 25

C-terminal modification: Not found

N-terminal modification : Free

Non-natural peptide information: None

Assay type : MTT-assay

Assay time : 4h

Activity : LD50 : 10 – 15 μg/ml

Cell line : HT29/219

Cancer type : Colon carcinoma

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2637.1296 Dalton

Aliphatic index : 0.86

Instability index : 27.076

Hydrophobicity (GRAVY) : -0.164

Isoelectric point : 9.9043

Charge (pH 7) : 4.7353

Aromaticity : 0.04

Molar extinction coefficient (cysteine, cystine): (0, 125)

Hydrophobic/hydrophilic ratio : 1.08333333

hydrophobic moment : -0.535

Missing amino acid : R,W,H,T,P,M,I,E,D,Y

Most occurring amino acid : K

Most occurring amino acid frequency : 5

Least occurring amino acid : F

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.4, 0.2, 0.2)

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

1 : Ghavami S, et al. Brevinin-2R(1) semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway. J Cell Mol Med. 2008; 12:1005-22. doi: 10.1111/j.1582-4934.2008.00129.x

Paper title : Brevinin-2R(1) semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway.

Doi : https://doi.org/10.1111/j.1582-4934.2008.00129.x

Abstract : Brevinin-2R is a novel non-hemolytic defensin that was isolated from the skin of the frog Rana ridibunda. It exhibits preferential cytotoxicity towards malignant cells, including Jurkat (T-cell leukemia), BJAB (B-cell lymphoma), HT29/219, SW742 (colon carcinomas), L929 (fibrosarcoma), MCF-7 (breast adenocarcinoma), A549 (lung carcinoma), as compared to primary cells including peripheral blood mononuclear cells (PBMC), T cells and human lung fibroblasts. Jurkat and MCF-7 cells overexpressing Bcl2, and L929 and MCF-7 over-expressing a dominant-negative mutant of a pro-apoptotic BNIP3 (DeltaTM-BNIP3) were largely resistant towards Brevinin-2R treatment. The decrease in mitochondrial membrane potential (DeltaPsim), or total cellular ATP levels, and increased reactive oxygen species (ROS) production, but not caspase activation or the release of apoptosis-inducing factor (AIF) or endonuclease G (Endo G), were early indicators of Brevinin-2R-triggered death. Brevinin-2R interacts with both early and late endosomes. Lysosomal membrane permeabilization inhibitors and inhibitors of cathepsin-B and cathepsin-L prevented Brevinin-2R-induced cell death. Autophagosomes have been detected upon Brevinin-2R treatment. Our results show that Brevinin-2R activates the lysosomalmitochondrial death pathway, and involves autophagy-like cell death.