Peptide name : TAT-Ras-GAP317-326

Source/Organism : Not found

Linear/Cyclic : Linear

Chirality : L

Peptide length: 22

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information: None

Assay type : LDH leakage assay

Assay time : 16 to 24h

Activity : 15% apoptosis at 10 µM

Cell line : HeLa

Cancer type : Cervical cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2814.2451 Dalton

Aliphatic index : 0.309

Instability index : 123.554

Hydrophobicity (GRAVY) : -2.013

Isoelectric point : 12

Charge (pH 7) : 7.7623

Aromaticity : 0.090

Molar extinction coefficient (cysteine, cystine): (11000, 11000)

Hydrophobic/hydrophilic ratio : 0.57142857

hydrophobic moment : 0.3659

Missing amino acid : C,H,P,I,E,F,S,Y,A

Most occurring amino acid : R

Most occurring amino acid frequency : 7

Least occurring amino acid : Q

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.1, 0.2, 0.2)

SMILES Notation: CSCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CN)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)[C@@H](C)O)[C@@H](C)O)C(C)C

1 : Michod D, et al. A RasGAP-derived cell permeable peptide potently enhances genotoxin-induced cytotoxicity in tumor cells. Oncogene. 2004; 23:8971-8. doi: 10.1038/sj.onc.1207999

Paper title : A RasGAP-derived cell permeable peptide potently enhances genotoxin-induced cytotoxicity in tumor cells.

Doi : https://doi.org/10.1038/sj.onc.1207999

Abstract : Treatment of many cancers relies on the combined action of several genotoxins, but the detrimental effect of these drugs on normal cells can cause severe side effects. One major challenge in anticancer therapy is therefore to increase the selectivity of current treatments toward cancer cells in order to spare normal cells. We have recently demonstrated that a RasGAP caspase cleavage fragment is able to sensitize HeLa cells towards cisplatin-induced apoptosis. Here, we extend this observation by showing that this fragment also enhances cell death induced by adriamycin and mitoxantrone, two other widely used genotoxins. Furthermore, we have delineated a short sequence within this fragment that still bears the genotoxin-sensitization property. The peptide encoded by this sequence, when fused to the TAT cell permeation sequence, potently sensitized a number of tumors cells, but not normal cells, towards apoptosis induced by cisplatin, adriamycin and mitoxantrone. This sensitization effect was not mediated through modulation of NFkappaB activity or activation of the JNK and p38 MAPK pathways. Our results demonstrate the feasibility in enhancing the efficacy of currently used drugs to selectively kill cancer cells using peptides derived from pro-apoptotic caspase substrate fragments.