title: Alternate PNA-DNA chimeras (PNA-DNA)(n): synthesis, binding properties and biological activity.
abstract: Peptide nucleic acids (PNAs) are oligonucleotide mimics in which the sugar-phosphate backbone has been replaced by a pseudo-peptide backbone. Among PNA-based molecules, PNA-DNA conjugates characterized by tracts of DNA bound to N and/or C terminus of PNA are very soluble in aqueous media, are able to recognize exclusively single strands of DNA and RNA in antiparallel fashion, activate RNAse H, bind to transcription factors and are more stable than DNA to nucleases degradation. Very little information is available on chimeras constituted of alternating monomers of PNA and DNA. In this article, we describe a simple fully automated strategy for the synthesis of 6-mer and 10-mer alternate PNA-DNA chimeras consisting of polythymine oligomers, stability assays in fetal calf serum, UV and CD studies of the single strand alternate chimeras and of alternate chimera/DNA and alternate chimera/RNA duplexes. Evidences supporting the formation of duplex hybrids were found. Furthermore, the ability of forming Hoogsteen base pairing with duplex DNA was investigated. Finally, we tested the ability of the PNA-DNA alternates in (a) interfering with reverse transcription of eukaryotic mRNA and (b) inhibiting DNA-protein interactions.
authors.affiliation: Dipartimento di Scienze Ambientali, Seconda Università di Napoli, via Vivaldi 43, 81100 Caserta, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Moggio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romanelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bianchi
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Enrica
authors.initials: E
authors.lastname: Fabbri
authors.forename: Irene
authors.initials: I
authors.lastname: Mancini
authors.forename: Benedetto
authors.initials: B
authors.lastname: di Blasio
authors.forename: Carlo
authors.initials: C
authors.lastname: Pedone
authors.forename: Anna
authors.initials: A
authors.lastname: Messere
mesh_terms: D000818:Animals; D020029:Base Pairing / Q000187:drug effects; D001665:Binding Sites; D002417:Cattle; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002942:Circular Dichroism / Q000379:methods; D004247:DNA / Q000037:antagonists & inhibitors / Q000737:chemistry*; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005057:Eukaryotic Cells / Q000737:chemistry; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011506:Proteins / Q000037:antagonists & inhibitors; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013941:Thymine / Q000737:chemistry; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D020135:Peptide Nucleic Acids; D011506:Proteins; D012333:RNA, Messenger; D012313:RNA; D004247:DNA; D013941:Thymine