Peptide name : E5

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 22

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : CCK-8 assay

Assay time : 24-h

Activity : 49% cell viability at 100 μM

Cell line : 4T1

Cancer type : Breast Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 2613.9536 Dalton

Aliphatic index : 0.663

Instability index : 64.8364

Hydrophobicity (GRAVY) : -0.545

Isoelectric point : 11.400

Charge (pH 7) : 2.7556

Aromaticity : 13.63

Molar extinction coefficient (cysteine, cystine): (1, 0)

Hydrophobic/hydrophilic ratio : 1

hydrophobic moment : 0.3438

Missing amino acid : A,E,H,K,M,P,W,Y

Most occurring amino acid : R

Most occurring amino acid frequency : 5

Least occurring amino acid : S

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (9.0, 31., 36.)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)CN)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)C(C)C)[C@@H](C)O

1 : Guo H, et al. Targeting the CXCR4/CXCL12 axis with the peptide antagonist E5 to inhibit breast tumor progression. Signal Transduct Target Ther. 2017; 2:17033. doi: 10.1038/sigtrans.2017.33

Paper title : Targeting the CXCR4/CXCL12 axis with the peptide antagonist E5 to inhibit breast tumor progression.

Doi : https://doi.org/10.1038/sigtrans.2017.33

Abstract : Emerging evidence has demonstrated that stromal cell-derived factor 1 (SDF-1) and its cognate receptor CXCR4 have critical roles in tumorigenesis, angiogenesis and metastasis. In this study, we demonstrated the significant inhibitory effects of a novel chemically synthetic peptide (E5) on the CXCR4/CXCL12 axis in breast cancer both in vitro and in vivo. E5 was capable of specifically binding to the murine breast cancer cell line 4T1, remarkably inhibiting CXCL12- or stromal cell (MS-5)-induced migration, and adhesion and sensitizing 4T1 cells to multiple chemotherapeutic drugs. Furthermore, E5 combined with either paclitaxel or cyclophosphamide significantly inhibited tumor growth in a breast cancer model. Mechanistic studies implied that E5 can inhibit the expression of CXCR4 to block the CXCL12-mediated recruitment of endothelial progenitor cells and repress CXCR4 downstream of the Akt and Erk signaling pathway, which are involved in tumor angiogenesis and progression. Further pharmacokinetic evaluation suggested that E5 has an acceptable stability, with a half-life of 10 h in healthy mice. In conclusion, E5 demonstrates a promising anti-tumor effect and could be a potential chemotherapeutic sensitizer to improve current clinical breast cancer therapies.