Peptide name : BIM BH3 (I155R, E158S)

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 : MTT assay

Assay time : 4h

Activity : Not found

Cell line : Not found

Cancer type : Prostate cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2614.8705 Dalton

Aliphatic index : 0.7

Instability index : 113.871

Hydrophobicity (GRAVY) : -0.914

Isoelectric point : 8.6842

Charge (pH 7) : 0.8387

Aromaticity : 0.190

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

Hydrophobic/hydrophilic ratio : 0.75

hydrophobic moment : 0.6983

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

Most occurring amino acid : R

Most occurring amino acid frequency : 4

Least occurring amino acid : W

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.2, 0.1, 0.3)

SMILES Notation: CC[C@H](C)[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(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)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 : Kim JS, et al. Conversion of cell-survival activity of Akt into apoptotic death of cancer cells by two mutations on the BIM BH3 domain. Cell Death Dis. 2015; 6:e1804. doi: 10.1038/cddis.2015.118

Paper title : Conversion of cell-survival activity of Akt into apoptotic death of cancer cells by two mutations on the BIM BH3 domain.

Doi : https://doi.org/10.1038/cddis.2015.118

Abstract : Survival and proliferation of cancer cells are often associated with hyperactivity of the serine/threonine kinase, Akt. Herein, we show that prosurvival activity of Akt can be converted into prodeath activity by embedding an Akt recognition sequence in the apoptogenic BH3 domain of human BIM. The recognition sequence was created by introducing two mutations, I155R and E158S, into the core region of the BIM BH3 domain. Although a 21-mer BIM BH3 peptide containing these two mutations bound weakly to BCL-XL and BCL-2, this peptide with phosphorylation of Ser158 bound to these proteins with a dissociation constant of <10 nM. The crystal structure of the phosphorylated peptide bound to BCL-XL revealed that the phospho-Ser158 makes favorable interactions with two BCL-XL residues, which cannot be formed with unphosphorylated Ser158. Remarkably, the designed peptide showed a cytotoxic effect on PTEN-null PC3 tumor cells whose Akt activity is aberrantly high. The cell-killing activity disappeared when the cellular Akt activity was lowered by ectopic PTEN expression. Thus, these results lay a foundation for developing a peptide or protein agent that is dormant in normal cells but is transformed into a potent apoptogenic molecule upon phosphorylation by hyperactivity of Akt in cancer cells.