Peptide name : NAF-1

Source/Organism : NAF-1/CISD2

Linear/Cyclic : Linear

Chirality : L

Peptide length: 24

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : Not Available

Assay time :

Activity : IC50 = 18.3 ± 0.4 μM

Cell line : MDA-MB-231

Cancer type : Breast Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 2728.3658 Dalton

Aliphatic index : 1.3

Instability index : 47.9958

Hydrophobicity (GRAVY) : 0.3333

Isoelectric point : 10.582

Charge (pH 7) : 4.7551

Aromaticity : 12.5

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

Hydrophobic/hydrophilic ratio : 2

hydrophobic moment : 0.3595

Missing amino acid : C,D,E,H,I,M,N,S,T,W

Most occurring amino acid : L

Most occurring amino acid frequency : 6

Least occurring amino acid : Y

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (50, 16., 45.)

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)Cc1ccccc1)C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)O)C(C)C

1 : Sohn YS, et al. A peptide-derived strategy for specifically targeting the mitochondria and ER of cancer cells: a new approach in fighting cancer. Chem Sci. 2022; 13:6929-6941. doi: 10.1039/d2sc01934e

Paper title : A peptide-derived strategy for specifically targeting the mitochondria and ER of cancer cells: a new approach in fighting cancer.

Doi : https://doi.org/10.1039/d2sc01934e

Abstract : An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance. Here, we present a new approach in cancer therapy that specifically targets the mitochondria and ER of cancer cells. We developed a peptide derived from the flexible and transmembrane domains of the human protein NAF-1/CISD2. This peptide (NAF-144-67) specifically permeates through the plasma membranes of human epithelial breast cancer cells, abolishes their mitochondria and ER, and triggers cell death with characteristics of apoptosis, ferroptosis and necroptosis. In vivo analysis revealed that the peptide significantly decreases tumor growth in mice carrying xenograft human tumors. Computational simulations of cancer vs. normal cell membranes reveal that the specificity of the peptide to cancer cells is due to its selective recognition of their membrane composition. NAF-144-67 represents a promising anti-cancer lead compound that acts via a unique mechanism.