Peptide name : MCL-1, BH3 (208-228)

Source/Organism : Anti apoptotic (MCL-1, BFL1)

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 : Not found

Cancer type : Skin cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2397.6484 Dalton

Aliphatic index : 0.742

Instability index : 47.8048

Hydrophobicity (GRAVY) : -0.852

Isoelectric point : 8.7506

Charge (pH 7) : 0.853

Aromaticity : 0.047

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

Hydrophobic/hydrophilic ratio : 0.75

hydrophobic moment : -0.926

Missing amino acid : C,W,P,M,I,S,Y

Most occurring amino acid : R

Most occurring amino acid frequency : 3

Least occurring amino acid : K

Least occurring amino acid frequency : 1

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

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](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](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O

1 : Stewart ML, et al. The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer. Nat Chem Biol. 2010; 6:595-601. doi: 10.1038/nchembio.391

Paper title : The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer.

Doi : https://doi.org/10.1038/nchembio.391

Abstract : The development of selective inhibitors for discrete anti-apoptotic BCL-2 family proteins implicated in pathologic cell survival remains a formidable but pressing challenge. Such precisely tailored compounds would serve as molecular probes and targeted therapies to study and treat human diseases driven by specific anti-apoptotic blockades. In particular, MCL-1 has emerged as a major resistance factor in human cancer. By screening a library of stabilized alpha-helix of BCL-2 domains (SAHBs), we determined that the MCL-1 BH3 helix is itself a potent and exclusive MCL-1 inhibitor. X-ray crystallography and mutagenesis studies defined key binding and specificity determinants, including the capacity to harness the hydrocarbon staple to optimize affinity while preserving selectivity. MCL-1 SAHB directly targets MCL-1, neutralizes its inhibitory interaction with pro-apoptotic BAK and sensitizes cancer cells to caspase-dependent apoptosis. By leveraging nature's solution to ligand selectivity, we generated an MCL-1-specific agent that defines the structural and functional features of targeted MCL-1 inhibition.