Structure-uptake relationship study of trimeric cell-penetrating peptides with different arrangements

Tat trimers are superior carriers for the delivery of exogenous biomolecules into living cells. We synthesized three Tat trimers carrying the same number of positive charges but with different arrangements of mono-Tat on the scaffold. We investigated the structure-uptake relationship of the three Tat trimers and found that tri-Tat 3 formed by mono-Tat arranged in the same orientation on the scaffold had lower cytotoxicity and better cellular uptake. We hope that this study will provide insight into the structural design and optimization of cell-penetrating peptides.