Peptide name : BIM FW1

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

Linear/Cyclic : Linear

Chirality : L

Peptide length: 23

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 : Leukemia

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2806.1433 Dalton

Aliphatic index : 0.808

Instability index : 75.1043

Hydrophobicity (GRAVY) : -0.730

Isoelectric point : 9.9708

Charge (pH 7) : 1.762

Aromaticity : 0.173

Molar extinction coefficient (cysteine, cystine): (13980, 13980)

Hydrophobic/hydrophilic ratio : 1.09090909

hydrophobic moment : -0.813

Missing amino acid : C,H,M,K,S,F,V

Most occurring amino acid : R

Most occurring amino acid frequency : 4

Least occurring amino acid : P

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.2, 0.2, 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)CNC(=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](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCNC(=N)N)[C@@H](C)CC)[C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]c2ccccc12)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)[C@@H](C)O

1 : Dutta S, et al. Peptide ligands for pro-survival protein Bfl-1 from computationally guided library screening. ACS Chem Biol. 2013; 8:778-88. doi: 10.1021/cb300679a

Paper title : Peptide ligands for pro-survival protein Bfl-1 from computationally guided library screening.

Doi : https://doi.org/10.1021/cb300679a

Abstract : Pro-survival members of the Bcl-2 protein family inhibit cell death by binding short helical BH3 motifs in pro-apoptotic proteins. Mammalian pro-survival proteins Bcl-x(L), Bcl-2, Bcl-w, Mcl-1, and Bfl-1 bind with varying affinities and specificities to native BH3 motifs, engineered peptides, and small molecules. Biophysical studies have determined interaction patterns for these proteins, particularly for the most-studied family members Bcl-x(L) and Mcl-1. Bfl-1 is a pro-survival protein implicated in preventing apoptosis in leukemia, lymphoma, and melanoma. Although Bfl-1 is a promising therapeutic target, relatively little is known about its binding preferences. We explored the binding of Bfl-1 to BH3-like peptides by screening a peptide library that was designed to sample a high degree of relevant sequence diversity. Screening using yeast-surface display led to several novel high-affinity Bfl-1 binders and to thousands of putative binders identified through deep sequencing. Further screening for specificity led to identification of a peptide that bound to Bfl-1 with K(d) < 1 nM and very slow dissociation from Bfl-1 compared to other pro-survival Bcl-2 family members. A point mutation in this sequence gave a peptide with ~50 nM affinity for Bfl-1 that was selective for Bfl-1 in equilibrium binding assays. Analysis of engineered Bfl-1 binders deepens our understanding of how the binding profiles of pro-survival proteins differ and may guide the development of targeted Bfl-1 inhibitors.