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Bioconjug Chem. 2011 Nov 16;22(11):2339-44. doi: 10.1021/bc200421z. Epub 2011 Oct 13.

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

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Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.


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.

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