Peptide name : RB4

Source/Organism : Derived from protein PLP2

Linear/Cyclic : Linear

Chirality : L

Peptide length: 24

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : MTT assay

Assay time : 24-h

Activity : EC50 = 0.427 ± 0.053 mol/L × 10-3

Cell line : U-87

Cancer type : Brain Tumor

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 2658.9896 Dalton

Aliphatic index : 0.329

Instability index : 66.2583

Hydrophobicity (GRAVY) : -0.579

Isoelectric point : 8.9382

Charge (pH 7) : 1.4835

Aromaticity : 8.333

Molar extinction coefficient (cysteine, cystine): (2, 1)

Hydrophobic/hydrophilic ratio : 1

hydrophobic moment : 0.6711

Missing amino acid : H,I,Q,V,Y

Most occurring amino acid : A

Most occurring amino acid frequency : 4

Least occurring amino acid : M

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (33., 29., 20.)

SMILES Notation: CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)O)[C@@H](C)O)[C@@H](C)O

1 : Maia VSC, et al. PLP2-derived peptide Rb4 triggers PARP-1-mediated necrotic death in murine melanoma cells. Sci Rep. 2022; 12:2890. doi: 10.1038/s41598-022-06429-8

Paper title : PLP2-derived peptide Rb4 triggers PARP-1-mediated necrotic death in murine melanoma cells.

Doi : https://doi.org/10.1038/s41598-022-06429-8

Abstract : Malignant melanoma is the main cause of death in patients with skin cancer. Overexpression of Proteolipid protein 2 (PLP2) increased tumor metastasis and the knockdown of PLP2 inhibited the growth and metastasis of melanoma cells. In the present work, we studied the antitumor activity of peptide Rb4 derived from protein PLP2. In vitro, Rb4 induced F-actin polymerization, prevented F-actin depolymerization and increased the ER-derived cytosolic calcium. Such effects were associated with necrosis of murine melanoma B16F10-Nex2 cells and with inhibition of the viability of human cancer cell lines. Loss of plasma membrane integrity, dilation of mitochondria, cytoplasm vacuolation and absence of chromatin condensation characterized tumor cell necrosis. Cleavage of PARP-1 and inhibition of RIP1 expression were also observed. In vivo, peptide Rb4 reduced the lung metastasis of tumor cells and delayed the subcutaneous melanoma growth in a syngeneic model. Rb4 induced the expression of two DAMPs molecules, HMGB1 and calreticulin, in B16F10-Nex2. Our results suggest that peptide Rb4 acts directly on tumor cells inducing the expression of DAMPs, which trigger the immunoprotective effect in vivo against melanoma cells. We suggest that peptide Rb4 is a promising compound to be developed as an anticancer drug.