Peptide name : A specific Eps8/EGFR Inhibitor Peptide 327

Source/Organism : A specific Eps8/EGFR Inhibitor Peptide 327

Linear/Cyclic : Not found

Chirality : Not found

Peptide length: 9

C-terminal modification: Not found

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Lactate dehydrogenase (LDH)-release assay

Assay time : 12h

Activity : IC50 : 119.84 ± 16.01 μM

Cell line : A549

Cancer type : Human lung cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 1176.3401 Dalton

Aliphatic index : 0.433

Instability index : 8.8889

Hydrophobicity (GRAVY) : 0.0333

Isoelectric point : 4.3704

Charge (pH 7) : -1.173

Aromaticity : 0.333

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

Hydrophobic/hydrophilic ratio : 1.25

hydrophobic moment : -1.218

Missing amino acid : R,W,H,T,P,M,I,S,Y,N,A,V,G

Most occurring amino acid : F

Most occurring amino acid frequency : 3

Least occurring amino acid : E

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.3, 0.1, 0.4)

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N)CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)O

1 : Xie X, et al. A dual-function epidermal growth factor receptor pathway substrate 8 (Eps8)-derived peptide exhibits a potent cytotoxic T lymphocyte-activating effect and a specific inhibitory activity. Cell Death Dis. 2018; 9:379. doi: 10.1038/s41419-018-0420-5

Paper title : A dual-function epidermal growth factor receptor pathway substrate 8 (Eps8)-derived peptide exhibits a potent cytotoxic T lymphocyte-activating effect and a specific inhibitory activity.

Doi : https://doi.org/10.1038/s41419-018-0420-5

Abstract : The identification and characterization of tumor-associated antigens (TAAs) that generate specific cytotoxic T lymphocytes (CTLs) are vital to the development of cancer immunotherapy. The epidermal growth factor receptor (EGFR) pathway substrate 8 gene (Eps8) is involved in regulating cancer progression and might be an ideal antigen. In this study, we searched for novel human leukocyte antigen (HLA)-A*2402-restricted epitopes derived from the Eps8 protein via the HLA-binding prediction algorithm. Among four candidates, peptides 327 (EFLDCFQKF), 534 (KYAKSKYDF) and 755 (LFSLNKDEL) induced peptide-specific CTLs to secrete higher levels of interferon-gamma (IFN-γ) and showed enhanced cytotoxic activity against malignant cancer cells. Our results demonstrated that peptide-specific CTLs showed effective antitumor responses, including upregulation of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), granzyme B and perforin. Treatment with peptide-sensitized peripheral blood mononuclear cells (PBMCs) significantly reduced the tumor growth in vivo compared with the non-peptide-sensitized PBMC treatment. Importantly, our results indicated that peptide 327 may interfere with EGFR signaling by mechanistically disrupting Eps8/EGFR complex formation. We extended this observation that peptide 327 also suppressed the viability of cancer cells, blocked EGFR signal pathway and reduced the expression of downstream targets. Notably, conjugation of peptide 327 to the TAT sequence (TAT-327) resulted in potent antitumor activity and selective insertion into cancer cell membranes, where it adopted a punctate distribution. Furthermore, peptide 327 and TAT-327 displayed anticancer properties in xenograft models. Our results indicated that 327, 534 and 755 were novel HLA-A*2402-restricted epitopes from Eps8. By inhibiting the Eps8/EGFR interaction, peptide 327 and TAT-327 may serve as novel peptide inhibitors, which could provide an innovative approach for treating various cancers.