Peptide name : NRC-13

Source/Organism : Skin mucous secretion of winter flounder

Linear/Cyclic : Linear

Chirality : L

Peptide length: 23

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information: None

Assay type : MTT/MTS assay

Assay time : 24h

Activity : 5-10% Cytotoxic at 25 µM

Cell line : 4T1

Cancer type : Breast cancer

Other activity : Anti-microbial activity

Amino acid composition bar chart :

Molecular mass : 2653.2151 Dalton

Aliphatic index : 1.187

Instability index : 14.3261

Hydrophobicity (GRAVY) : -0.178

Isoelectric point : 10.295

Charge (pH 7) : 4.8441

Aromaticity : 0.087

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

Hydrophobic/hydrophilic ratio : 1.09090909

hydrophobic moment : 0.1537

Missing amino acid : C,Q,P,M,I,F,S,D,N

Most occurring amino acid : L

Most occurring amino acid frequency : 5

Least occurring amino acid : W

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.5, 0.0, 0.4)

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CN)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)C(=O)O

1 : Hilchie AL, et al. Pleurocidin-family cationic antimicrobial peptides are cytolytic for breast carcinoma cells and prevent growth of tumor xenografts. Breast Cancer Res. 2011; 13:R102. doi: 10.1186/bcr3043

Paper title : Pleurocidin-family cationic antimicrobial peptides are cytolytic for breast carcinoma cells and prevent growth of tumor xenografts.

Doi : https://doi.org/10.1186/bcr3043

Abstract : INTRODUCTION: Cationic antimicrobial peptides (CAPs) defend against microbial pathogens; however, certain CAPs also exhibit anticancer activity. The purpose of this investigation was to determine the effect of the pleurocidin-family CAPs, NRC-03 and NRC-07, on breast cancer cells. METHODS: MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) and acid phosphatase cell-viability assays were used to assess NRC-03- and NRC-07-mediated killing of breast carcinoma cells. Erythrocyte lysis was determined with hemolysis assay. NRC-03 and NRC-07 binding to breast cancer cells and normal fibroblasts was assessed with fluorescence microscopy by using biotinylated-NRC-03 and -NRC-07. Lactate dehydrogenase-release assays and scanning electron microscopy were used to evaluate the effect of NRC-03 and NRC-07 on the cell membrane. Flow-cytometric analysis of 3,3'-dihexyloxacarbocyanine iodide- and dihydroethidium-stained breast cancer cells was used to evaluate the effects of NRC-03 and NRC-07 on mitochondrial membrane integrity and reactive oxygen species (ROS) production, respectively. Tumoricidal activity of NRC-03 and NRC-07 was evaluated in NOD SCID mice bearing breast cancer xenografts. RESULTS: NRC-03 and NRC-07 killed breast cancer cells, including drug-resistant variants, and human mammary epithelial cells but showed little or no lysis of human dermal fibroblasts, umbilical vein endothelial cells, or erythrocytes. Sublethal doses of NRC-03 and, to a lesser extent, NRC-07 significantly reduced the median effective concentration (EC50) of cisplatin for breast cancer cells. NRC-03 and NRC-07 bound to breast cancer cells but not fibroblasts, suggesting that killing required peptide binding to target cells. NRC-03- and NRC-07-mediated killing of breast cancer cells correlated with expression of several different anionic cell-surface molecules, suggesting that NRC-03 and NRC-07 bind to a variety of negatively-charged cell-surface molecules. NRC-03 and NRC-07 also caused significant and irreversible cell-membrane damage in breast cancer cells but not in fibroblasts. NRC-03- and NRC-07-mediated cell death involved, but did not require, mitochondrial membrane damage and ROS production. Importantly, intratumoral administration of NRC-03 and NRC-07 killed breast cancer cells grown as xenografts in NOD SCID mice. CONCLUSIONS: These findings warrant the development of stable and targeted forms of NRC-03 and/or NRC-07 that might be used alone or in combination with conventional chemotherapeutic drugs for the treatment of breast cancer.