Inhibiting the Toxicity of Curcumin with Tetraarginine-tetratyrosin Cell-penetrating Peptide on Jurkat T-cells

Curcumin is a member of the curcuminoid family and the most important active ingredient in turmeric. Despite its wide therapeutic and biological benefits, curcumin often cannot be an effective therapeutic agent due to its hydrophobic nature and as a result low solubility, and its use is limited. In order to overcome this issue, in this study, a cell penetrating amphipathic peptide with FAM-YYYYRRRR sequence was prepared by solid phase synthesis method and RP-HPLC method was used to purify the peptide. The tetra-tyrosine as a hydrophobic moiety of the peptide binds to curcumin, while the tetra-arginine with four positive charges–which is highly hydrophilic and electrostatically charged– moiety increases the solubility of the peptide/curcumin complex and at the same time enhance its cellular permeability. The three-dimensional structure of the mentioned peptide in PEP-FOLD-4 design and peptide-curcumin interaction was investigated in MVD v.6, which shows a suitable score of -108.4. The binding of peptide to curcumin was calculated spectroscopically by plotting the binding isotherm curve and using OriginLab software. The binding constant of peptide to curcumin is reported as 3×105 M-1. The toxicity effect of curcumin alone and the peptide/curcumin complex separately on Jurkat T-cells was assayed by MTT test and showed that the toxicity of the peptide in the complex with curcumin is significantly reduced on the cells. Therefore, the peptide protects T cells upon binding with curcumin