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.
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.
Cogoi
Susanna
S
Department of Biomedical Science and Technology, School of Medicine, P.le Kolbe 4, 33100 Udine, Italy.
Paramasivam
Manikandan
M
Filichev
Vyacheslav
V
Géci
Imrich
I
Pedersen
Erik B
EB
Xodo
Luigi E
LE
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*
C507245:(R)-1-O-(4-(1-pyrenylethynyl)phenylmethyl)glycerol; D011721:Pyrenes; C030984:pyrene; D005990:Glycerol