Peptide name : PTPRJ-pep19.5

Source/Organism : PTPRJ agonist peptides

Linear/Cyclic : Cyclic(C1-C9)

Chirality : L

Peptide length: 9

C-terminal modification: Cyclic(C1-C9)

N-terminal modification : Free

Non-natural peptide information: None

Assay type : Trypan blue assay

Assay time : 48h

Activity : 2 ± 1.5% cell growth inhibition at 160 µM

Cell line : HeLa

Cancer type : Cervical cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 993.0813 Dalton

Aliphatic index : 0.222

Instability index : 120.244

Hydrophobicity (GRAVY) : -0.577

Isoelectric point : 7.0018

Charge (pH 7) : 0.0018

Aromaticity : 0

Molar extinction coefficient (cysteine, cystine): (0, 125)

Hydrophobic/hydrophilic ratio : 0.8

hydrophobic moment : 1.1059

Missing amino acid : R,W,Q,P,M,I,E,K,S,D,Y,F,L,V,G

Most occurring amino acid : H

Most occurring amino acid frequency : 3

Least occurring amino acid : N

Least occurring amino acid frequency : 1

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

SMILES Notation: C[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](N)CS)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)O)[C@@H](C)O

1 : Ortuso F, et al. Discovery of PTPRJ agonist peptides that effectively inhibit in vitro cancer cell proliferation and tube formation. ACS Chem Biol. 2013; 8:1497-506. doi: 10.1021/cb3007192

Paper title : Discovery of PTPRJ agonist peptides that effectively inhibit in vitro cancer cell proliferation and tube formation.

Doi : https://doi.org/10.1021/cb3007192

Abstract : PTPRJ is a receptor protein tyrosine phosphatase involved in both physiological and oncogenic pathways. We previously reported that its expression is strongly reduced in the majority of explored cancer cell lines and tumor samples; moreover, its restoration blocks in vitro cancer cell proliferation and in vivo tumor formation. By means of a phage display library screening, we recently identified two peptides able to bind and activate PTPRJ, resulting in cell growth inhibition and apoptosis of both cancer and endothelial cells. Here, on a previously discovered PTPRJ agonist peptide, PTPRJ-pep19, we synthesized and assayed a panel of nonapeptide analogues with the aim to identify specific amino acid residues responsible for peptide activity. These second-generation nonapeptides were tested on both cancer and primary endothelial cells (HeLa and HUVEC, respectively); interestingly, one of them (PTPRJ-19.4) was able to both dramatically reduce cell proliferation and effectively trigger apoptosis of both HeLa and HUVECs compared to its first-generation counterpart. Moreover, PTPRJ-pep19.4 significantly inhibited in vitro tube formation on Matrigel. Intriguingly, while ERK1/2 phosphorylation and cell proliferation were both inhibited by PTPRJ-pep19.4 in breast cancer cells (MCF-7 and SKBr3), no effects were observed on primary normal human mammary endothelial cells (HMEC). We further characterized these peptides by molecular modeling and NMR experiments reporting, for the most active peptide, the possibility of self-aggregation states and highlighting new hints of structure-activity relationship. Thus, our results indicate that this nonapeptide might represent a great potential lead for the development of novel targeted anticancer drugs.