Peptide name : D-N-Ter-Antp

Source/Organism : VDAC1(voltage-dependent anion channel1)

Linear/Cyclic : Linear

Chirality : Mix

Peptide length: 42

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : IC50 : 1.5 ± 0.6 µM

Cell line : CLL

Cancer type : Leukemia

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 4990.8541 Dalton

Aliphatic index : 0.581

Instability index : 36.169

Hydrophobicity (GRAVY) : -0.659

Isoelectric point : 10.748

Charge (pH 7) : 7.4946

Aromaticity : 0.166

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

Hydrophobic/hydrophilic ratio : 1.1

hydrophobic moment : -0.431

Missing amino acid : C,H,E

Most occurring amino acid : K

Most occurring amino acid frequency : 6

Least occurring amino acid : S

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](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O

1 : Prezma T, et al. VDAC1-based peptides: novel pro-apoptotic agents and potential therapeutics for B-cell chronic lymphocytic leukemia. Cell Death Dis. 2013; 4:e809. doi: 10.1038/cddis.2013.316

Paper title : VDAC1-based peptides: novel pro-apoptotic agents and potential therapeutics for B-cell chronic lymphocytic leukemia.

Doi : https://doi.org/10.1038/cddis.2013.316

Abstract : The voltage-dependent anion channel 1 (VDAC1), localized in the outer mitochondrial membrane, mediates metabolic cross-talk between the mitochondrion and the cytoplasm and thus serves a fundamental role in cell energy metabolism. VDAC1 also plays a key role in mitochondria-mediated apoptosis, interacting with anti-apoptotic proteins. Resistance of cancer cells to apoptosis involves quenching the mitochondrial apoptotic pathway by over-expression of anti-apoptotic/pro-survival hexokinase (HK) and Bcl-2 family proteins, proteins that mediate their anti-apoptotic activities via interaction with VDAC1. Using specifically designed VDAC1-based cell-penetrating peptides, we targeted these anti-apoptotic proteins to prevent their pro-survival/anti-apoptotic activities. Anti-apoptotic proteins are expressed at high levels in B-cell chronic lymphocytic leukemia (CLL), an incurable disease requiring innovative new approaches to improve therapeutic outcome. CLL is characterized by a clonal accumulation of mature neoplastic B cells that are resistant to apoptosis. Specifically, we demonstrate that the VDAC1-based peptides (Antp-LP4 and N-Terminal-Antp) selectively kill peripheral blood mononuclear cells (PBMCs) obtained from CLL patients, yet spare those obtained from healthy donors. The cell death induction competence of the peptides was well correlated with the amount of double positive CD19/CD5 cancerous CLL PBMCs, further illustrating their selectivity toward cancer cells. Moreover, these VDAC1-based peptides induced apoptosis by activating the mitochondria-mediated pathway, reflected in membrane blebbing, condensation of nuclei, DNA fragmentation, release of mitochondrial cytochrome c, loss of mitochondrial membrane potential, decreased cellular ATP levels and detachment of HK, all leading to apoptotic cell death. Thus, the mode of action of the peptides involves decreasing energy production and inducing apoptosis. Over 27 versions of cell-penetrating VDAC1-based peptides were designed and screened to identify the most stable, short and apoptosis-inducing peptides toward CLL-derived lymphocytes. In this manner, three optimized peptides suitable for in vivo studies were identified. This study thus reveals the potential of VDAC1-based peptides as an innovative and effective anti-CLL therapy.