Peptide name : Bax 9

Source/Organism : Effectors (BAK, BAX)

Linear/Cyclic : Linear

Chirality : L

Peptide length: 18

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : IC50 : 148.0 μmol/L

Cell line : HL-60

Cancer type : Not specified

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2079.3985 Dalton

Aliphatic index : 0.866

Instability index : 74.6333

Hydrophobicity (GRAVY) : -0.855

Isoelectric point : 6.2064

Charge (pH 7) : -0.2449

Aromaticity : 0

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

Hydrophobic/hydrophilic ratio : 0.7

hydrophobic moment : -1.698

Missing amino acid : W,H,Q,T,P,F,Y,N,A,V

Most occurring amino acid : K

Most occurring amino acid frequency : 3

Least occurring amino acid : C

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.5, 0.3, 0.2)

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

1 : Shangary S, et al. Sequence and helicity requirements for the proapoptotic activity of Bax BH3 peptides. Mol Cancer Ther. 2004; 3:1343-54.

Paper title : Sequence and helicity requirements for the proapoptotic activity of Bax BH3 peptides.

Doi : https://doi.org/Not available

Abstract : Overexpression of the antiapoptotic proteins Bcl-2 and Bcl-XL is commonly observed in human malignancies and contributes to chemotherapy and radiation resistance. Bcl-2 and Bcl-XL inhibit apoptosis by binding to proapoptotic proteins such as Bax, thereby preventing chemotherapy-induced or radiation-induced release of cytochrome c from mitochondria and subsequent activation of the caspase protease cascade. Efforts to inhibit Bcl-2 or Bcl-XL function in tumor cells have focused on developing agents to inhibit the interactions of these proteins with proapoptotic proteins. Peptides derived from the BH3 domains of proapoptotic proteins have been shown to disrupt the interactions of Bcl-2 and Bcl-XL with key binding partners in cell-free reactions and to promote cellular apoptosis. However, less is known about the targets of BH3 peptides in intact cells as well as the sequence, length, and conformational requirements for peptide biological activity. In this report, we show that cell-permeable Bax BH3 peptides physically disrupt Bax/Bcl-2 heterodimerization in intact cells and that this disruption correlates with peptide-induced cell death. A point-mutant, control peptide that failed to disrupt intracellular Bax/Bcl-2 interactions also failed to promote apoptosis. To determine important sequence, length, and structural requirements for peptide activity, we generated and systematically analyzed the biological activities of 17 Bax BH3 peptide variants. Peptides were quantitatively examined for their ability to inhibit Bax/Bcl-2 and Bax/Bcl-XL heterodimerization in vitro and to promote cytochrome c release from mitochondria isolated from Jurkat, HL-60, U937, and PC-3 cells. Our results define 15 amino acids as the minimal length required for Bax BH3 peptide biological activity and show that amino acids COOH terminal to the BH3 core sequence are less critical than those located NH2 terminal to the core. In addition, circular dichroism spectroscopy revealed that high alpha-helical content generally correlated with, but was not sufficient for, peptide activity. Taken together, these studies provide a basis for future optimization of Bax BH3 peptide as a therapeutic anticancer agent.