Efficient cellular delivery of β-Galactosidase mediated by NrTPs, a new family of cell-penetrating peptides

Rodrigues, Margarida; de la Torre, Beatriz G.; Rádis-Baptista, Gandhi; Santos, Nuno C.; Andreu, David

http://hdl.handle.net/10451/6747

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Authors

Rodrigues, Margarida

de la Torre, Beatriz G.

Rádis-Baptista, Gandhi

Santos, Nuno C.

Andreu, David

Abstract(s)

Nucleolar targeting peptides (NrTPs), a recently developed family of cell-penetrating peptides, have been shown to be very efficient in entering cells and accumulating in their nucleoli. In this work, we have used conjugates of NrTP6 (YKQSHKKGGKKGSG) covalently linked to β-galactosidase in order to demonstrate the capacity of NrTP for intracellular delivery of large molecules. NrTP6/β-galactosidase conjugates, prepared by maleimide-based chemistry, were stable and enzymatically active on the standard 4-methylumbelliferyl β-D-galactopyranoside substrate. Their translocation into HeLa cells, monitored by β-galactosidase activity as a readout of the uptake, showed efficient cellular entry and thus demonstrated the potential of NrTPs for intracellular delivery of large-size cargos with preservation of biological activity.