title: γ Sulphate PNA (PNA S): highly selective DNA binding molecule showing promising antigene activity.
abstract: Peptide Nucleic Acids (PNAs), nucleic acid analogues showing high stability to enzyme degradation and strong affinity and specificity of binding toward DNA and RNA are widely investigated as tools to interfere in gene expression. Several studies have been focused on PNA analogues with modifications on the backbone and bases in the attempt to overcome solubility, uptake and aggregation issues. γ PNAs, PNA derivatives having a substituent in the γ position of the backbone show interesting properties in terms of secondary structure and affinity of binding toward complementary nucleic acids. In this paper we illustrate our results obtained on new analogues, bearing a sulphate in the γ position of the backbone, developed to be more DNA-like in terms of polarity and charge. The synthesis of monomers and oligomers is described. NMR studies on the conformational properties of monomers and studies on the secondary structure of single strands and triplexes are reported. Furthermore the hybrid stability and the effect of mismatches on the stability have also been investigated. Finally, the ability of the new analogue to work as antigene, interfering with the transcription of the ErbB2 gene on a human cell line overexpressing ErbB2 (SKBR3), assessed by FACS and qPCR, is described.
authors.affiliation: Dipartimento delle Scienze Biologiche, Facoltà di Scienze Biotecnologiche, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Avitabile
authors.forename: Loredana
authors.initials: L
authors.lastname: Moggio
authors.forename: Gaetano
authors.initials: G
authors.lastname: Malgieri
authors.forename: Domenica
authors.initials: D
authors.lastname: Capasso
authors.forename: Sonia
authors.initials: S
authors.lastname: Di Gaetano
authors.forename: Michele
authors.initials: M
authors.lastname: Saviano
authors.forename: Carlo
authors.initials: C
authors.lastname: Pedone
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romanelli
mesh_terms: D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D009696:Nucleic Acids / Q000737:chemistry* / Q000378:metabolism; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D013431:Sulfates / Q000737:chemistry*
chemical_list: D004268:DNA-Binding Proteins; D009696:Nucleic Acids; D020135:Peptide Nucleic Acids; D018719:Erb-b2 Receptor Tyrosine Kinases; D013431:Sulfates; C508053:ERBB2 protein, human