title: Gramicidin A-based peptide vector for intracellular protein delivery.
abstract: 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.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, Miklukho-Maklaya, 16/10, 117997 Moscow, Russia. stoilova@transfection.ru
authors.forename: Tatiana B
authors.initials: TB
authors.lastname: Stoilova
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Kovalchuk
authors.forename: Natalya S
authors.initials: NS
authors.lastname: Egorova
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Surovoy
authors.forename: Vadim T
authors.initials: VT
authors.lastname: Ivanov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability; D016503:Drug Delivery Systems; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism*; D006096:Gramicidin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D006096:Gramicidin; D001616:beta-Galactosidase