Peptide name : IP3R-derived peptide (IDP)

Source/Organism : Not found

Linear/Cyclic : Linear

Chirality : L

Peptide length: 20

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 : CLL

Cancer type : Leukemia

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2304.6608 Dalton

Aliphatic index : 1.41

Instability index : 21.885

Hydrophobicity (GRAVY) : 0.26

Isoelectric point : 4.5581

Charge (pH 7) : -1.2468

Aromaticity : 0.05

Molar extinction coefficient (cysteine, cystine): (1490, 1490)

Hydrophobic/hydrophilic ratio : 1

hydrophobic moment : -0.874

Missing amino acid : W,H,Q,M,F,A,G

Most occurring amino acid : V

Most occurring amino acid frequency : 3

Least occurring amino acid : Y

Least occurring amino acid frequency : 1

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

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)O)C(C)C)C(C)C)[C@@H](C)CC

1 : Zhong F, et al. Induction of Ca²+-driven apoptosis in chronic lymphocytic leukemia cells by peptide-mediated disruption of Bcl-2-IP3 receptor interaction. Blood. 2011; 117:2924-34. doi: 10.1182/blood-2010-09-307405

Paper title : Induction of Ca²+-driven apoptosis in chronic lymphocytic leukemia cells by peptide-mediated disruption of Bcl-2-IP3 receptor interaction.

Doi : https://doi.org/10.1182/blood-2010-09-307405

Abstract : Bcl-2 contributes to the pathophysiology and therapeutic resistance of chronic lymphocytic leukemia (CLL). Therefore, developing inhibitors of this protein based on a thorough understanding of its mechanism of action is an active and promising area of inquiry. One approach centers on agents (eg, ABT-737) that compete with proapoptotic members of the Bcl-2 protein family for binding in the hydrophobic groove formed by the BH1-BH3 domains of Bcl-2. Another region of Bcl-2, the BH4 domain, also contributes to the antiapoptotic activity of Bcl-2 by binding to the inositol 1,4,5-trisphosphate receptor (IP₃R) Ca²(+) channel, inhibiting IP(3)-dependent Ca²(+) release from the endoplasmic reticulum. We report that a novel synthetic peptide, modeled after the Bcl-2-interacting site on the IP₃R, binds to the BH4 domain of Bcl-2 and functions as a competitive inhibitor of the Bcl-2-IP₃R interaction. By disrupting the Bcl-2-IP₃R interaction, this peptide induces an IP₃R-dependent Ca²(+) elevation in lymphoma and leukemia cell lines and in primary CLL cells. The Ca²(+) elevation evoked by this peptide induces apoptosis in CLL cells, but not in normal peripheral blood lymphocytes, suggesting the involvement of the Bcl-2-IP₃R interaction in the molecular mechanism of CLL and indicating the potential merit of targeting this interaction therapeutically.