title: Identification of a new G-quadruplex motif in the KRAS promoter and design of pyrene-modified G4-decoys with antiproliferative activity in pancreatic cancer cells.
abstract: A new quadruplex motif located in the promoter of the human KRAS gene, within a nuclease hypersensitive element (NHE), has been characterized. Oligonucleotides mimicking this quadruplex are found to compete with a DNA-protein complex between NHE and a nuclear extract from pancreatic cancer cells. When modified with (R)-1-O-[4-1-(1-pyrenylethynyl) phenylmethyl]glycerol insertions (TINA), the quadruplex oligonucleotides showed a dramatic increase of the T(m) (deltaT(m) from 22 to 32 degrees C) and a strong antiproliferative effects in Panc-1 cells.
authors.affiliation: Department of Biomedical Science and Technology, School of Medicine, P.le Kolbe 4, 33100 Udine, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Cogoi
authors.forename: Manikandan
authors.initials: M
authors.lastname: Paramasivam
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Filichev
authors.forename: Imrich
authors.initials: I
authors.lastname: Géci
authors.forename: Erik B
authors.initials: EB
authors.lastname: Pedersen
authors.forename: Luigi E
authors.initials: LE
authors.lastname: Xodo
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D024202:Electrophoretic Mobility Shift Assay; D054856:G-Quadruplexes; D011905:Genes, ras; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011401:Promoter Regions, Genetic; D011721:Pyrenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C507245:(R)-1-O-(4-(1-pyrenylethynyl)phenylmethyl)glycerol; D011721:Pyrenes; C030984:pyrene; D005990:Glycerol