Peptide name : C16-E4Y

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 5

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : WST-8 assay

Assay time : 24-h

Activity : 50 % cell viability at 0.05 wt %

Cell line : HepG-2

Cancer type : Liver Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 697.6445 Dalton

Aliphatic index : 0

Instability index : 203.6

Hydrophobicity (GRAVY) : -3.06

Isoelectric point : 4.05

Charge (pH 7) : -4.1557

Aromaticity : 20

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

Hydrophobic/hydrophilic ratio : 0

hydrophobic moment : -0.469

Missing amino acid : A,C,D,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W

Most occurring amino acid : E

Most occurring amino acid frequency : 4

Least occurring amino acid : Y

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (80, 0, 20)

SMILES Notation: N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O

1 : Morita K, et al. In Situ Synthesis of an Anticancer Peptide Amphiphile Using Tyrosine Kinase Overexpressed in Cancer Cells. JACS Au. 2022; 2:2023-2028. doi: 10.1021/jacsau.2c00301

Paper title : In Situ Synthesis of an Anticancer Peptide Amphiphile Using Tyrosine Kinase Overexpressed in Cancer Cells.

Doi : https://doi.org/10.1021/jacsau.2c00301

Abstract : Cell-selective killing using molecular self-assemblies is an emerging concept for cancer therapy. Reported molecular self-assemblies are triggered by hydrolysis of well-designed molecules inside or outside cancer cells. This hydrolysis can occur in cancer and normal cells because of the abundance of water in living systems. Here, we report the in situ synthesis of a self-assembling molecule using a tyrosine kinase overexpressed in cancer cells. We designed a tyrosine-containing peptide amphiphile (C16-E4Y) that is transformed into a phosphorylated peptide amphiphile (C16-E4pY) by the overexpressed tyrosine kinase. Phosphorylation of C16-E4Y promoted self-assembly to form nanofibers in cancer cells. C16-E4Y exhibited selective cytotoxicity toward cancer cells overexpressing the tyrosine kinase. Self-assembled C16-E4pY induced endoplasmic reticulum stress that caused apoptotic cell death. Animal experiments revealed that C16-E4Y has antitumor activity. These results show that an enzyme overexpressed in cancer cells is available for intracellular synthesis of an antitumor self-assembling drug that is cell-selective.