Peptide name : MccJ25-18-4

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : Mix

Peptide length: Not available

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information: x = Norleucine

Assay type : MTT assay

Assay time : 48-h

Activity : IC50 = 25.0 ± 0.5 μM

Cell line : MDA-MB-435-MDR

Cancer type : Breast Cancer

Other activity : Antimicrobial

Amino Acid Composition Bar Chart : Not available

Molecular mass : Not available

Aliphatic index : Not available

Instability index : Not available

Hydrophobicity (GRAVY) : Not available

Isoelectric point : Not available

Charge (pH 7) : Not available

Aromaticity : Not available

Molar extinction coefficient (cysteine, cystine): Not available

Hydrophobic/hydrophilic ratio : Not available

hydrophobic moment : Not available

Missing amino acid : Not available

Most occurring amino acid : Not available

Most occurring amino acid frequency : Not available

Least occurring amino acid : Not available

Least occurring amino acid frequency : Not available

3D-structure: Not available

Secondary structure fraction (Helix, Turn, Sheet): Not available

SMILES Notation: Not available

Molecular descriptors: Not available

ADMET properties: Not available

1 : Soudy R, et al. Breast Cancer Targeting Peptide Binds Keratin 1: A New Molecular Marker for Targeted Drug Delivery to Breast Cancer. Mol Pharm. 2017; 14:593-604. doi: 10.1021/acs.molpharmaceut.6b00652

Paper title : Breast Cancer Targeting Peptide Binds Keratin 1: A New Molecular Marker for Targeted Drug Delivery to Breast Cancer.

Doi : https://doi.org/10.1021/acs.molpharmaceut.6b00652

Abstract : The biomarkers or receptors expressed on cancer cells and the targeting ligands with high binding affinity for biomarkers play a key role in early detection and treatment of breast cancer. The breast cancer targeting peptide p160 (12-mer) and its enzymatically stable analogue 18-4 (10-mer) showed marked potential for breast cancer drug delivery using cell studies and animal models. Herein, we used affinity purification, liquid chromatography-tandem mass spectrometry, and proteomics to identify keratin 1 (KRT1) as the target receptor highly expressed on breast cancer cells for p160 peptide(s). Western blot and immunocytochemistry in MCF-7 breast cancer cells confirmed the identity of KRT1. We demonstrate that the p160 or 18-4 binding to MCF-7 breast cancer cells is dependent on the expression of KRT1, and we confirm peptide-KRT1 binding specificity using SPR experiments (K_d ∼ 1.1 μM and 0.98 μM for p160 and 18-4, respectively). Furthermore, we assessed the ability of peptide 18-4 to improve the cellular uptake and anticancer activity of a pro-apoptotic antimicrobial peptide, microcin J25 (MccJ25), in breast cancer cells. A covalent conjugate of peptide 18-4 with MccJ25 showed preferential cytotoxicity toward breast cancer cells with minimal cytotoxicity against normal HUVEC cells. The conjugate inhibited the growth of MDA-MB-435 MDR multidrug-resistant cells with an IC₅₀ comparable to that of nonresistant cells. Conjugation improved selective cellular uptake of MccJ25, and the conjugate triggered cancer cell death by apoptosis. Our findings establish KRT1 as a new marker for breast cancer targeting. Additionally, it pinpoints the potential use of antimicrobial lasso peptides as a novel class of anticancer therapeutics.