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Biochim Biophys Acta. 2008 Oct;1778(10):2026-31. doi: 10.1016/j.bbamem.2008.01.029. Epub 2008 Feb 21.

Gramicidin A-based peptide vector for intracellular protein delivery.

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Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, Miklukho-Maklaya, 16/10, 117997 Moscow, Russia.


The development of the peptide-based vectors for the intracellular delivery of biologically active macromolecules has opened new prospects of their application in research and therapy. Earlier the amphipathic cell-penetrating peptide (CPP) Pep-1 was reported to mediate cellular uptake of proteins without covalent binding to them. In this work we studied the ability of a series of membrane-active amphipathic peptides, based on the gramicidin A sequence, to transport a model protein across the eukaryotic cell membrane. Among them the positively charged Cys-containing peptide P10C demonstrated the most effective beta-galactosidase intracellular delivery. Besides, this peptide was shown to form noncovalent associates with beta-galactosidase as judged from electrophoresis and enzymatic activity assays. In addition, a series of new gramicidin analogues were prepared and the effect of N-terminus modification of gramicidin on the protein transduction efficiency was studied.

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