Peptide name : IL13Rα2 D1 peptide

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 12

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : MTT assay

Assay time : 48-h

Activity : inhibited IL13-stimulated cell adhesion

Cell line : KM12SM

Cancer type : Colorectal Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 1377.5419 Dalton

Aliphatic index : 0.65

Instability index : 12.6917

Hydrophobicity (GRAVY) : -0.833

Isoelectric point : 8.5911

Charge (pH 7) : 0.7609

Aromaticity : 8.333

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

Hydrophobic/hydrophilic ratio : 0.5

hydrophobic moment : 0.5892

Missing amino acid : A,C,D,F,H,L,M,P,Q,R,V,Y

Most occurring amino acid : T

Most occurring amino acid frequency : 3

Least occurring amino acid : G

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (25, 24., 50)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)CN)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)O)[C@@H](C)O)[C@@H](C)CC

1 : Bartolomé RA, et al. An IL13Rα2 peptide exhibits therapeutic activity against metastatic colorectal cancer. Br J Cancer. 2018; 119:940-949. doi: 10.1038/s41416-018-0259-7

Paper title : An IL13Rα2 peptide exhibits therapeutic activity against metastatic colorectal cancer.

Doi : https://doi.org/10.1038/s41416-018-0259-7

Abstract : BACKGROUND: Interleukin 13 receptor α2 (IL13Rα2) is overexpressed in metastatic colorectal cancer. Here, we have developed novel strategies to block IL-13 binding to IL13Rα2 in order to reduce metastatic spread. METHODS: Synthetic IL13Rα2 D1 peptide (GSETWKTIITKN) was tested for the inhibition of IL-13 binding to IL13Rα2 using ELISA and different cellular assays. Peptide blocking effects on different cell signalling mediators were determined by western blot. An enantiomer version of the peptide (D-D1) was prepared to avoid proteolytic digestion. Nude mice were used for tumour growth and survival analysis after treatment with IL13Rα2 peptides. RESULTS: IL13Rα2 D1 peptide inhibited migration, invasion, and proliferation in metastatic colorectal and glioblastoma cancer cells treated with IL-13. Residues 82K, 83T, 85I and 86T were essential for blocking IL-13. IL13Rα2 peptide abolished ligand-mediated receptor internalisation and degradation, and substantially decreased IL-13 signalling capacity through IL13Rα2 to activate the FAK, PI3K/AKT and Src pathways as well as MT1-MMP expression. In addition, D1 significantly inhibited IL-13-mediated STAT6 activation through IL13Rα1. Nude mice treated with the enantiomer D-D1 peptide showed a remarkable survival increase. CONCLUSIONS: We propose that the D-D1 peptide from IL13Rα2 represents a promising therapeutic agent to inhibit metastatic progression in colorectal cancer and, likely, other solid tumours.