Peptide name : TAT-CTMP4

Source/Organism : Not found

Linear/Cyclic : Linear

Chirality : L

Peptide length: 25

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : TAT-CTMP4 induced a dose-dependent increase in apoptosis as detected by %-TUNEL positive cells and %-active caspase-3 (% active caspase-3 ranged from 31.2 to 61.9 at the highest dose tested (10 µM).

Cell line : AsPC-1

Cancer type : Pancreatic cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2928.2963 Dalton

Aliphatic index : 0.664

Instability index : 74.74

Hydrophobicity (GRAVY) : -0.728

Isoelectric point : 4.4376

Charge (pH 7) : -2.2329

Aromaticity : 0.08

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

Hydrophobic/hydrophilic ratio : 0.78571428

hydrophobic moment : -0.375

Missing amino acid : C,W,H,I,Y,N,V

Most occurring amino acid : L

Most occurring amino acid frequency : 4

Least occurring amino acid : P

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.4, 0.2, 0.2)

SMILES Notation: CSCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)O)[C@@H](C)O

1 : Simon PO, et al. Targeting AKT with the proapoptotic peptide, TAT-CTMP: a novel strategy for the treatment of human pancreatic adenocarcinoma. Int J Cancer. 2009; 125:942-51. doi: 10.1002/ijc.24424

Paper title : Targeting AKT with the proapoptotic peptide, TAT-CTMP: a novel strategy for the treatment of human pancreatic adenocarcinoma.

Doi : https://doi.org/10.1002/ijc.24424

Abstract : Pancreatic adenocarcinoma carries an ominous prognosis and has little effective treatment. Several studies have demonstrated that the potently antiapoptotic phosphatidyl inositol 3'-kinase (PI3K)-protein kinase B/AKT pathway is active in pancreas cancer. A recent study identified an endogenous AKT antagonist, carboxyl terminal modulator protein (CTMP). CTMP inhibits the phosphorylation of AKT, preventing full activation of the kinase. We screened several cell permeable peptides from the N-terminal domain of CTMP (termed TAT-CTMP1-4) in vitro and found one that caused significant apoptosis in pancreatic adenocarcinoma cell lines. An inactive variant of this peptide was synthesized and used as a negative control. In all cell lines tested, TAT-CTMP4 induced a dose-dependent increase in apoptosis as detected by %-TUNEL positive cells and %-active caspase-3 (% active caspase-3 ranged from 31.2 to 61.9 at the highest dose tested (10 microM). A screening of various cell and tissue types revealed that the proapoptotic activity was highest in pancreatic adenocarcinoma. TAT-CTMP induced similar levels of active caspase-3 as several other known inducers of apoptosis: gemcitabine, radiation therapy, wortmannin and recombinant tumor necrosis factor (TNF)-alpha. No apoptosis was observed in donor human peripheral blood mononuclear cells (PBMC, p < 0.01). We further showed that TAT-CTMP4 could augment either gemcitabine chemotherapy or radiation therapy, standard therapies for pancreas cancer. Pancreatic adenocarcinoma xenografts treated with a single dose of TAT-CTMP4 demonstrated a marked increase in caspase-3 positive tumor cells when compared with untreated controls. Additionally, pancreatic adenocarcinoma allografts treated with intratumoral TAT-CTMP and systemic gemcitabine displayed a significantly smaller tumor burden while undergoing treatment than mice in control groups (p < 0.001). These data indicate that inhibiting AKT with CTMP may be of therapeutic benefit in the treatment of pancreatic adenocarcinoma and, when combined with established therapies, may result in an increase in tumor cell death.