Peptide name : R11-NLS-pep8

Source/Organism : NKp44 derived synthetic peptide

Linear/Cyclic : Linear

Chirality : Mix

Peptide length: 38

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : PrestoBlue assay

Assay time : 24-h

Activity : ED50 = 5.9 μM

Cell line : HepG-2

Cancer type : Liver Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 4787.7554 Dalton

Aliphatic index : 0.692

Instability index : 165.684

Hydrophobicity (GRAVY) : -1.452

Isoelectric point : 12

Charge (pH 7) : 17.7479

Aromaticity : 2.631

Molar extinction coefficient (cysteine, cystine): (1, 0)

Hydrophobic/hydrophilic ratio : 0.48

hydrophobic moment : 0.2301

Missing amino acid : D,F,G,H,M,N,Q,Y

Most occurring amino acid : R

Most occurring amino acid frequency : 14

Least occurring amino acid : W

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (28., 10., 26.)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)O)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C

1 : Shemesh A, et al. NKp44-Derived Peptide Binds Proliferating Cell Nuclear Antigen and Mediates Tumor Cell Death. Front Immunol. 2018; 9:1114. doi: 10.3389/fimmu.2018.01114

Paper title : NKp44-Derived Peptide Binds Proliferating Cell Nuclear Antigen and Mediates Tumor Cell Death.

Doi : https://doi.org/10.3389/fimmu.2018.01114

Abstract : Proliferating cell nuclear antigen (PCNA) is considered as a hub protein and is a key regulator of DNA replication, repair, cell cycle control, and apoptosis. PCNA is overexpressed in many cancer types, and PCNA overexpression is correlated with cancer virulence. Membrane-associated PCNA is a ligand for the NKp44 (NCR2) innate immune receptor. The purpose of this study was to characterize the PCNA-binding site within NKp44. We have identified NKp44-derived linear peptide (pep8), which can specifically interact with PCNA and partly block the NKp44-PCNA interaction. We then tested whether NKp44-derived pep8 (NKp44-pep8) fused to cell-penetrating peptides (CPPs) can be employed for targeting the intracellular PCNA for the purpose of anticancer therapy. Treatment of tumor cells with NKp44-pep8, fused to R11-NLS cell-penetrating peptide (R11-NLS-pep8), reduced cell viability and promoted cell death, in various murine and human cancer cell lines. Administration of R11-NLS-pep8 to tumor-bearing mice suppressed tumor growth in the 4T1 breast cancer and the B16 melanoma in vivo models. We therefore identified the NKp44 binding site to PCNA and further developed an NKp44-peptide-based agent that can inhibit tumor growth through interfering with the function of intracellular PCNA in the tumor cell.