Peptide name : Bim

Source/Organism : BH3-only, Direct activators, BIM analogues

Linear/Cyclic : Linear

Chirality : L

Peptide length: 21

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : Not found

Cell line : EL4

Cancer type : Mouse T cell lymphoma

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2613.8791 Dalton

Aliphatic index : 0.885

Instability index : 81.4667

Hydrophobicity (GRAVY) : -0.614

Isoelectric point : 4.8712

Charge (pH 7) : -1.1585

Aromaticity : 0.190

Molar extinction coefficient (cysteine, cystine): (8480, 8480)

Hydrophobic/hydrophilic ratio : 0.90909090

hydrophobic moment : 0.8712

Missing amino acid : C,H,T,P,M,K,S,V

Most occurring amino acid : E

Most occurring amino acid frequency : 3

Least occurring amino acid : W

Least occurring amino acid frequency : 1

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

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](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](NC(=O)[C@@H](N)CCC(=O)O)[C@@H](C)CC)[C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O

1 : Kashiwagi H, et al. TAT-Bim induces extensive apoptosis in cancer cells. Ann Surg Oncol. 2007; 14:1763-71. doi: 10.1245/s10434-006-9298-z

Paper title : TAT-Bim induces extensive apoptosis in cancer cells.

Doi : https://doi.org/10.1245/s10434-006-9298-z

Abstract : BACKGROUND: Suppression of apoptosis is central to the development of cancer and is associated with resistance to modern adjuvant treatments. Therefore, molecules and pathways of apoptotic processes are critical targets for the development of anti-cancer therapeutics. Since apoptosis is executed by intracellular proteins, molecular approaches must incorporate a method to deliver the treatment into the tumor cells. METHODS: We utilized a peptide that contains two domains, a peptide transduction domain derived from the HIV-1 TAT protein and a biological effector domain, the BH3 domain from the pro-apoptotic Bcl-2 family member Bim. We examined whether this construct (TAT-Bim) induced apoptosis in several cancer cell lines (T-cell lymphoma (EL4), pancreatic cancer (Panc-02), and melanoma (B16)) and whether TAT-Bim treatment synergized with radiation. A mutant TAT-Bim peptide with no biologic activity (TAT-Bim-inactive) was used as a control. C57/BL6 mice were challenged with syngeneic cancer cell lines and the effects of intratumoral TAT-Bim injection on tumor growth and host survival were determined. RESULTS: TAT-Bim was internalized by all cancer cells within two hours. TAT-Bim resulted in apoptosis in a dose dependent fashion in all cell lines and sublethal irradiation augmented the effects of TAT-Bim induced apoptosis. TAT-Bim significantly slowed tumor growth in murine models of pancreatic cancer and melanoma. CONCLUSION: TAT-Bim exemplifies a strategy for cancer therapy that involves inducing apoptosis by antagonizing the endogenous anti-apoptotic machinery. Small peptide therapeutics, in combination with traditional adjuvant therapies such as radiation, may provide a valuable 'second hit' and drive tumor cells into programmed cell death.