Branched dimerization of Tat peptide improves permeability to HeLa and hippocampal neuronal cells.
A dimeric branched peptide TATp-D designed as an analogue of the HIV-Tat protein transduction domain (TATp), a prototypical cell penetrating peptide (CPP), demonstrates significantly enhanced cell uptake at 0.25 to 2.5 μM. Live cell confocal laser scanning microscopy revealed that multivalency dramatically improved the permeation potency of TATp-D to HeLa and primary hippocampal neuronal cells. The observed enhanced ability of TATp-D to translocate through the membrane is highlighted by a non-linear dependence on concentration, exhibiting the greatest uptake at sub-micromolar concentrations as compared to TATp. Multimerization via bis-Fmoc Lysine offered a synthetically straightforward method to investigate the effects of multivalent CPPs while offering orthogonal handles for cargo attachment, increasing the utility of CPPs at significantly lower concentrations.
Department of Chemistry, Washington State University, Pullman, Washington 99164, USA. jonel.saludes@wsu.edu.
I Abrrey
IA
Monreal
Qian
Q
Liu
Katherine
K
Tyson
Tyler
T
Bland
Doralyn S
DS
Dalisay
Erin V
EV
Adams
Gary A
GA
Wayman
Hector C
HC
Aguilar
Jonel P
JP
Saludes
D002463:Cell Membrane Permeability; D006367:HeLa Cells; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D008968:Molecular Conformation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D055503:Protein Multimerization; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000378:metabolism*
D054322:tat Gene Products, Human Immunodeficiency Virus