Peptide name : 8Dap

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: Not available

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information: X = 2,3-Diaminopropionic Acid , Z = norleucine

Assay type : WST-1 assay

Assay time : 24-h

Activity : EC50 = 61.4±0.7 μM

Cell line : PANC-1

Cancer type : Pancreatic Cancer

Other activity : Anticancer

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 : Tanishiki N, et al. Endowment of pH Responsivity to Anticancer Peptides by Introducing 2,3-Diaminopropionic Acid Residues. Chembiochem. 2019; 20:2109-2117. doi: 10.1002/cbic.201900226

Paper title : Endowment of pH Responsivity to Anticancer Peptides by Introducing 2,3-Diaminopropionic Acid Residues.

Doi : https://doi.org/10.1002/cbic.201900226

Abstract : Endowment of pH responsivity to anticancer peptides is a promising approach to achieve better selectivity to cancer tissues. In this research, a template peptide was designed based on magainin 2, an antimicrobial peptide with anticancer activity, and a series of peptides were designed by replacing different numbers of lysine with the unnatural amino acid, 2,3diaminopropionic acid (Dap), which has a positive charge at weakly acidic pH in cancer tissues, but is neutral at physiological pH 7.4. These Dap-containing peptides are expected to interact more strongly with tumor cells than with normal cells because 1) weakly acidic conditions form in tumors, and 2) the membrane of tumor cells is more anionic than that of normal cells. Although all examined peptides showed potent cytotoxicities to multidrug-resistant cancer cells at a weakly acidic pH (ED₅₀ ≈5 μm), the toxicity decreased with an increase in the number of Dap at pH 7.4 (8 Dap residues resulted in ED₅₀ ≈60 μm). Furthermore, the introduction of Dap reduced cytotoxicity against normal cells. Thus, Dap led to significantly improved cancer targeting due to a pH-dependent charge shift. Fluorescence imaging and model membrane experiments supported this charge-shift model.