title: Signal peptide mimics conjugated to peptide nucleic acid: a promising solution for improving cell membrane permeability.
abstract: The specific binding ability and biostability of PNA (peptide nucleic acid) with DNA or RNA make PNA not only a good tool for the studies of molecular biology but also the candidate for gene-targeting drugs. However, the main obstacle for its potential usage as a therapeutic is the low cell uptake caused by the poor cell membrane permeability. In this paper the hydrophobic pentadecapeptide and two signal peptide mimics, hexa- and decapeptides ending with a positively charged amino acid, were proposed as the linked carrier for the transportation of PNA T10 through the cell membrane; stable spin label was coupled to the peptide-PNA conjugate so that the ESR measurements can be used for the assessment of their transmembrane movements. The syntheses of spin-labeled peptide-PNA conjugates were carried out on MBHA resin with Boc strategy. The cell membrane permeability of the spin-labeled conjugates of peptides and PNA can be determined with ESR, during the incubation of erythrocyte with the samples. According to ESR measurements, the three conjugates exhibit enhanced uptake into erythrocytes. The hexa- and decapeptide-modified PNA showed suitable water solubility. The peptide-PNA conjugates retained their binding ability to complementary DNA. The results suggest that peptide modification of PNA might be a promising solution for improving cell membrane permeability toward PNA.
authors.affiliation: National Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, P. R. China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Li
authors.forename: Liangren
authors.initials: L
authors.lastname: Zhang
authors.forename: Jingfen
authors.initials: J
authors.lastname: Lu
authors.forename: Yaozu
authors.initials: Y
authors.lastname: Chen
authors.forename: Jimei
authors.initials: J
authors.lastname: Min
authors.forename: Lihe
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D002463:Cell Membrane Permeability; D004247:DNA / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004578:Electron Spin Resonance Spectroscopy; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018716:Molecular Mimicry; D020135:Peptide Nucleic Acids / Q000737:chemistry* / Q000493:pharmacokinetics; D021382:Protein Sorting Signals; D012995:Solubility; D013113:Spin Labels
chemical_list: D004337:Drug Carriers; D020135:Peptide Nucleic Acids; D021382:Protein Sorting Signals; D013113:Spin Labels; D004247:DNA