Peptide name : [Lys6] TG

Source/Organism : Trichogin GA

Linear/Cyclic : Linear

Chirality : L

Peptide length: Not available

C-terminal modification: Linear

N-terminal modification : Lol = leucinol

Non-natural peptide information: U = 2-Aminoisobutyric acid

Assay type : MTT assay

Assay time : 24-h

Activity : EC50 = 4 µM

Cell line : T-67

Cancer type : Brain Tumor

Other activity : AMP, 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 : Dalzini A, et al. The rational search for selective anticancer derivatives of the peptide Trichogin GA IV: a multi-technique biophysical approach. Sci Rep. 2016; 6:24000. doi: 10.1038/srep24000

Paper title : The rational search for selective anticancer derivatives of the peptide Trichogin GA IV: a multi-technique biophysical approach.

Doi : https://doi.org/10.1038/srep24000

Abstract : Peptaibols are peculiar peptides produced by fungi as weapons against other microorganisms. Previous studies showed that peptaibols are promising peptide-based drugs because they act against cell membranes rather than a specific target, thus lowering the possibility of the onset of multi-drug resistance, and they possess non-coded α-amino acid residues that confer proteolytic resistance. Trichogin GA IV (TG) is a short peptaibol displaying antimicrobial and cytotoxic activity. In the present work, we studied thirteen TG analogues, adopting a multidisciplinary approach. We showed that the cytotoxicity is tuneable by single amino-acids substitutions. Many analogues maintain the same level of non-selective cytotoxicity of TG and three analogues are completely non-toxic. Two promising lead compounds, characterized by the introduction of a positively charged unnatural amino-acid in the hydrophobic face of the helix, selectively kill T67 cancer cells without affecting healthy cells. To explain the determinants of the cytotoxicity, we investigated the structural parameters of the peptides, their cell-binding properties, cell localization, and dynamics in the membrane, as well as the cell membrane composition. We show that, while cytotoxicity is governed by the fine balance between the amphipathicity and hydrophobicity, the selectivity depends also on the expression of negatively charged phospholipids on the cell surface.