Issue 25, 2015

Branched dimerization of Tat peptide improves permeability to HeLa and hippocampal neuronal cells

Abstract

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.

Graphical abstract: Branched dimerization of Tat peptide improves permeability to HeLa and hippocampal neuronal cells

Supplementary files

Article information

Article type
Communication
Submitted
03 ⴱⵕⴰ 2015
Accepted
23 ⴱⵕⴰ 2015
First published
23 ⴱⵕⴰ 2015

Chem. Commun., 2015,51, 5463-5466

Author version available

Branched dimerization of Tat peptide improves permeability to HeLa and hippocampal neuronal cells

I. A. Monreal, Q. Liu, K. Tyson, T. Bland, D. S. Dalisay, E. V. Adams, G. A. Wayman, H. C. Aguilar and J. P. Saludes, Chem. Commun., 2015, 51, 5463 DOI: 10.1039/C5CC00882D

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