title: Synthesis of conformationally preorganized and cell-permeable guanidine-based gamma-peptide nucleic acids (gammaGPNAs).
abstract: A general method for preparing optically pure guanidine-based gamma-peptide nucleic acid (gammaGPNA) monomers for all four natural nucleobases (A, C, G, and T) is described. These second-generation gammaGPNAs differ from the first-generation GPNAs in that the guanidinium group is installed at the gamma- instead of the alpha-position of the N-(2-aminoethyl)glycine backbone unit. This positional switch enables GPNAs to be synthesized from relatively cheap L- as opposed to D-amino acids. Unlike their alpha-predecessors, which are randomly folded, gammaGPNAs prepared from L-amino acids are preorganized into a right-handed helix and bind to DNA and RNA with exceptionally high affinity and sequence selectivity and are readily taken up by mammalian cells.
authors.affiliation: Department of Chemistry and Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Bichismita
authors.initials: B
authors.lastname: Sahu
authors.forename: Venugopal
authors.initials: V
authors.lastname: Chenna
authors.forename: Kira L
authors.initials: KL
authors.lastname: Lathrop
authors.forename: Sufi M
authors.initials: SM
authors.lastname: Thomas
authors.forename: Gerald
authors.initials: G
authors.lastname: Zon
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Livak
authors.forename: Danith H
authors.initials: DH
authors.lastname: Ly
mesh_terms: D000818:Animals; D001483:Base Sequence; D002463:Cell Membrane Permeability; D004247:DNA / Q000378:metabolism; D019791:Guanidine / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008099:Liver / Q000166:cytology; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D020135:Peptide Nucleic Acids; D012313:RNA; D004247:DNA; D019791:Guanidine