Peptide name : P5317-28

Source/Organism : E3 ubiquitin-protein ligase

Linear/Cyclic : Linear

Chirality : L

Peptide length: 12

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information: None

Assay type : Immunoprecipitation assay

Assay time : Not found

Activity : IC50 : 4.7 µM

Cell line : HCT-116-p53+/+

Cancer type : Colon cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 1476.6711 Dalton

Aliphatic index : 0.975

Instability index : 64.2083

Hydrophobicity (GRAVY) : -0.35

Isoelectric point : 4.3703

Charge (pH 7) : -1.237

Aromaticity : 0.166

Molar extinction coefficient (cysteine, cystine): (5500, 5500)

Hydrophobic/hydrophilic ratio : 1

hydrophobic moment : -0.569

Missing amino acid : C,R,H,M,I,Y,N,A,V,G

Most occurring amino acid : L

Most occurring amino acid frequency : 3

Least occurring amino acid : Q

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.4, 0.2, 0.5)

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

1 : Shiheido H, et al. mRNA display selection of an optimized MDM2-binding peptide that potently inhibits MDM2-p53 interaction. PLoS One. 2011; 6:e17898. doi: 10.1371/journal.pone.0017898

Paper title : mRNA display selection of an optimized MDM2-binding peptide that potently inhibits MDM2-p53 interaction.

Doi : https://doi.org/10.1371/journal.pone.0017898

Abstract : p53 is a tumor suppressor protein that prevents tumorigenesis through cell cycle arrest or apoptosis of cells in response to cellular stress such as DNA damage. Because the oncoprotein MDM2 interacts with p53 and inhibits its activity, MDM2-p53 interaction has been a major target for the development of anticancer drugs. While previous studies have used phage display to identify peptides (such as DI) that inhibit the MDM2-p53 interaction, these peptides were not sufficiently optimized because the size of the phage-displayed random peptide libraries did not cover all of the possible sequences. In this study, we performed selection of MDM2-binding peptides from large random peptide libraries in two stages using mRNA display. We identified an optimal peptide named MIP that inhibited the MDM2-p53 and MDMX-p53 interactions 29- and 13-fold more effectively than DI, respectively. Expression of MIP fused to the thioredoxin scaffold protein in living cells by adenovirus caused stabilization of p53 through its interaction with MDM2, resulting in activation of the p53 pathway. Furthermore, expression of MIP also inhibited tumor cell proliferation in a p53-dependent manner more potently than DI. These results show that two-stage, mRNA-displayed peptide selection is useful for the rapid identification of potent peptides that target oncoproteins.