Peptide name : Akt-in

Source/Organism : Not found

Linear/Cyclic : Linear

Chirality : L

Peptide length: 15

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Co-immunoprecipitation, GST Pull-down,GST Competition, In Vitro Akt Kinase, PKA Kinase, In Vitro PDK1 Kinase, PtdIns(3,4,5)P3 Lipid-Protein Pull-down, Proliferation assay, Cell Death assay and Mitochondrial Permeability Transition assay

Assay time : Not found

Activity : Not found

Cell line : T4

Cancer type : T-cell Leukemia

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 1871.0585 Dalton

Aliphatic index : 0.586

Instability index : -2.5333

Hydrophobicity (GRAVY) : -0.786

Isoelectric point : 5.3826

Charge (pH 7) : -1.1129

Aromaticity : 0.2

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

Hydrophobic/hydrophilic ratio : 1.14285714

hydrophobic moment : 0.2789

Missing amino acid : C,Q,M,I,S,Y,N,G

Most occurring amino acid : A

Most occurring amino acid frequency : 2

Least occurring amino acid : V

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.3, 0.2, 0.4)

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)N)C(C)C)[C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)O

1 : Hiromura M, et al. Inhibition of Akt kinase activity by a peptide spanning the betaA strand of the proto-oncogene TCL1. J Biol Chem. 2004; 279:53407-18. doi: 10.1074/jbc.M403775200

Paper title : Inhibition of Akt kinase activity by a peptide spanning the betaA strand of the proto-oncogene TCL1.

Doi : https://doi.org/10.1074/jbc.M403775200

Abstract : Akt plays a central role in the regulation of cellular anti-apoptosis underlying various human neoplastic diseases. We have demonstrated previously that TCL1 (a proto-oncogene underlying human T cell prolymphocytic leukemia) interacts with Akt and functions as an Akt kinase co-activator. With the aim to develop an Akt kinase inhibitor, we hypothesized that a peptide, which spans the Akt-binding site, binds to Akt and modulates Akt kinase activity and its downstream biological responses. Indeed, we demonstrated that a peptide, named "Akt-in" (Akt inhibitor, NH(2)-AVTDHPDRLWAWEKF-COOH, encompassing the betaA strand of human TCL1), interacted with Akt and specifically inhibited its kinase activity. Nuclear magnetic resonance studies suggested that interaction of Akt-in with the pleckstrin homology domain (PH) of Akt caused conformational changes on the variable loop 1 of Akt, the locus mediating phosphoinositide binding. Consistently, interaction of Akt-in with the Akt PH domain prevented phosphoinositide binding and hence inhibited membrane translocation and activation of Akt. Moreover, Akt-in inhibited not only cellular proliferation and anti-apoptosis in vitro but also in vivo tumor growth without any adverse effect. The roles of Akt, which possesses a PH domain, in intracellular signaling were well established. Hence, Akt inhibitors create an attractive target for anticancer therapy. However, no effective inhibitors specific for Akt have been developed. Akt-in, which inhibits association of phosphatidylinositol with Akt, is the first molecule to demonstrate specific Akt kinase inhibition potency. This observation will facilitate the design of specific inhibitors for Akt, a core intracellular survival factor underlying various human neoplastic diseases.