Peptide name : BIM Y4eK- 18

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

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 : Not found

Cell line : Not found

Cancer type : Not specified

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2206.4563 Dalton

Aliphatic index : 0.544

Instability index : 35.9944

Hydrophobicity (GRAVY) : -0.727

Isoelectric point : 8.4304

Charge (pH 7) : 0.76

Aromaticity : 0.277

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

Hydrophobic/hydrophilic ratio : 1

hydrophobic moment : -0.465

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

Most occurring amino acid : Y

Most occurring amino acid frequency : 2

Least occurring amino acid : I

Least occurring amino acid frequency : 1

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

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

1 : Dutta S, et al. Potent and specific peptide inhibitors of human pro-survival protein Bcl-xL. J Mol Biol. 2015; 427:1241-1253. doi: 10.1016/j.jmb.2014.09.030

Paper title : Potent and specific peptide inhibitors of human pro-survival protein Bcl-xL.

Doi : https://doi.org/10.1016/j.jmb.2014.09.030

Abstract : The Bcl-2 family of proteins plays a critical role regulating apoptosis, and pro-survival Bcl-2 family members are important therapeutic targets due to their overexpression in different cancers. Pro-apoptotic Bcl-2 homology 3 (BH3)-only proteins antagonize pro-survival Bcl-2 protein functions by binding directly to them, and a sub-class of BH3-only proteins termed sensitizers can initiate apoptosis via this mechanism in response to diverse signals. The five pro-survival proteins Bcl-xL, Mcl-1, Bcl-2, Bcl-w and Bfl-1 differ in their binding preferences, with Bcl-xL, Bcl-2 and Bcl-w sharing similar interaction profiles for many natural sensitizers and small molecules. Peptides that bind selectively to just one or a subset of family members have shown utility in assays that diagnose apoptotic blockades in cancer cells and as reagents for dissecting apoptotic mechanism. Combining computational design, combinatorial library screening and rational mutagenesis, we designed a series of BH3 sensitizer peptides that bind Bcl-xL with sub-nanomolar affinity and selectivity up to 1000-fold over each of the four competing pro-survival proteins. We demonstrate the efficacy of our designed BH3 peptides in assays that differentiate between cancer cells that are dependent on different pro-survival proteins.