Peptide name : ATAP-iRGD-M8

Source/Organism : Anti apoptotic (MCL-1, BFL1)

Linear/Cyclic : Linear

Chirality : L

Peptide length: 38

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : MTT assay

Assay time : 48h

Activity : IC50 : 2.1 μM

Cell line : DU-145

Cancer type : Prostate cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 4336.0842 Dalton

Aliphatic index : 0.615

Instability index : 11.1526

Hydrophobicity (GRAVY) : -0.494

Isoelectric point : 8.7299

Charge (pH 7) : 1.744

Aromaticity : 0.105

Molar extinction coefficient (cysteine, cystine): (6990, 7115)

Hydrophobic/hydrophilic ratio : 1.11111111

hydrophobic moment : 0.3302

Missing amino acid : N,H

Most occurring amino acid : K

Most occurring amino acid frequency : 6

Least occurring amino acid : W

Least occurring amino acid frequency : 1

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

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)C(C)C)[C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)O

1 : De G, et al. Amphipathic tail-anchoring peptide is a promising therapeutic agent for prostate cancer treatment. Oncotarget. 2014; 5:7734-47. doi: 10.18632/oncotarget.2301

Paper title : Amphipathic tail-anchoring peptide is a promising therapeutic agent for prostate cancer treatment.

Doi : https://doi.org/10.18632/oncotarget.2301

Abstract : Amphipathic tail-anchoring peptide (ATAP) derived from the human anti-apoptotic protein Bfl-1 is a potent inducer of apoptosis by targeting mitochondria permeability transition. By linking ATAP to an internalizing RGD peptide (iRGD), selective targeting for ATAP to tumor cell was achieved. Confocal fluorescence microscopy showed that ATAP-iRGD could penetrate into cancer cells and distribute along the mitochondria network. ATAP-iRGD triggered mitochondria-dependent cell death through release of cytochrome c. In an effort to promote ATAP-iRGD physiochemical properties to approach clinic application, amino acid substitution and chemical modification were made with ATAP-iRGD to improve its bioactivity. One of these modified peptides, ATAP-iRGD-M8, was with improved stability and aqueous solubility without compromising in vitro cytotoxicity in cultured cancer cells. In vivo xenograft studies with multiple prostate cancer cell lines showed that intravenous administration of ATAP-iRGD-M8 suppressed tumor growth. Toxicological studies revealed that repetitive intravenous administration of ATAP-iRGD-M8 did not produce significant toxicity in the SV129 mice. Our data suggest that ATAP-iRGD-M8 is a promising agent with high selectivity and limited systemic toxicity for prostate cancer treatment.