Peptide name : CA4

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 35

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : MTT assay

Assay time : 48-h

Activity : Graph Figure 2

Cell line : U-251

Cancer type : Brain Tumor

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 3783.4175 Dalton

Aliphatic index : 0.14

Instability index : 38.5829

Hydrophobicity (GRAVY) : -0.565

Isoelectric point : 8.5208

Charge (pH 7) : 2.7701

Aromaticity : 5.714

Molar extinction coefficient (cysteine, cystine): (8, 4)

Hydrophobic/hydrophilic ratio : 1.5

hydrophobic moment : 0.6642

Missing amino acid : I,S,V,W,Y

Most occurring amino acid : C

Most occurring amino acid frequency : 8

Least occurring amino acid : H

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (19., 31., 14.)

SMILES Notation: CSCC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CS)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H](N)CS)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)NCC(=O)NCC(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O

1 : Xu T, et al. Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential. Sci Rep. 2016; 6:19799. doi: 10.1038/srep19799

Paper title : Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential.

Doi : https://doi.org/10.1038/srep19799

Abstract : Brain tumors are fast proliferating and destructive within the brain microenvironment. Effective chemotherapeutic strategies are currently lacking which combat this deadly disease curatively. The glioma-specific chloride ion channel represents a specific target for therapy. Chlorotoxin (CTX), a peptide derived from scorpion venom, has been shown to be specific and efficacious in blocking glioma Cl(-) channel activity. Here, we report on two new derivatives (termed CA4 and CTX-23) designed and generated on the basis of the peptide sequence alignments of CTX and BmKCT. The novel peptides CA4 and CTX-23 are both effective in reducing glioma cell proliferation. In addition, CTX, CA4 and CTX-23 impact on cell migration and spheroid migration. These effects are accompanied by diminished cell extensions and increased nuclear sizes. Furthermore, we found that CA4 and CTX-23 are selective with low toxicity against primary neurons and astrocytes. In the ex vivo VOGiM, which maintain the entire brain tumor microenvironment, both CTX and CA4 display anti-tumor activity and reduce tumor volume. Hence, CTX and CA4 reveal anti-angiogenic properties with endothelial and angiogenic hotspots disrupting activities. These data report on the identification of two novel CTX derivatives with multiple anti-glioma properties including anti-angiogenesis.