title: Synthesis of a dibromoperylene phosphoramidite building block and its incorporation at the 5' end of a G-quadruplex forming oligonucleotide: spectroscopic properties and structural studies of the resulting dibromoperylene conjugate.
abstract: Previous studies indicate that some perylene bisimide derivatives can drive the assembly of DNA G-quadruplexes, thus suggesting the possible advantage in the adoption of perylene-conjugated G-rich oligonucleotides in biological and biotechnological applications. Nevertheless, the typical poor solubility of perylene bisimides strongly limits the number of suitable chemical strategies to prepare perylene-conjugated oligonucleotides. In order to overcome these difficulties, we employed the earlier described core twisted perylene derivatives possessing unique optical and electronic properties, besides good solubility in common solvents. As a first result, the large-scale synthesis of a new dibromoperylene derivative (PEOEBr) phosphoramidite building block is herein reported. Furthermore, the structural behavior of the conjugated PEOEBr-GGGTTAGGG (HTRp2) human telomeric repeat was investigated by using CD, UV, fluorescence, and gel electrophoresis techniques in desalted water and in K(+)- and Na(+)-containing buffers. We observed that the peculiar property of PEOEBr moieties to form dimers instead of extended aggregates drives the HTRp2 strands toward dimerization and mainly promotes the formation of quadruplex species having both the 5'-ends located at the same side of the structures. However, the counterions present in solutions (K(+) or Na(+)) as well as the strand concentration, also contribute to influence the topology and the stoichiometry of formed structures. Furthermore, unlike the unmodified sequence GGGTTAGGG (HTR2), HTRp2 strands quickly associate into G-quadruplexes even in desalted water, as assessed by CD experiments.
authors.affiliation: Dipartimento di Chimica, Sapienza Università di Roma, Piazzale A. Moro 5, 00185 Roma, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Franceschin
authors.forename: Nicola
authors.initials: N
authors.lastname: Borbone
authors.forename: Giorgia
authors.initials: G
authors.lastname: Oliviero
authors.forename: Valentina
authors.initials: V
authors.lastname: Casagrande
authors.forename: Maria
authors.initials: M
authors.lastname: Scuotto
authors.forename: Teresa
authors.initials: T
authors.lastname: Coppola
authors.forename: Silvia
authors.initials: S
authors.lastname: Borioni
authors.forename: Luciano
authors.initials: L
authors.lastname: Mayol
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ortaggi
authors.forename: Armandodoriano
authors.initials: A
authors.lastname: Bianco
authors.forename: Jussara
authors.initials: J
authors.lastname: Amato
authors.forename: Michela
authors.initials: M
authors.lastname: Varra
mesh_terms: D001483:Base Sequence; D001966:Bromine / Q000737:chemistry; D002942:Circular Dichroism; D024202:Electrophoretic Mobility Shift Assay; D054856:G-Quadruplexes; D054879:Halogenation; D006801:Humans; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010569:Perylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013056:Spectrophotometry, Ultraviolet
chemical_list: D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D010569:Perylene; D001966:Bromine