The effect of INA [(R)-1-O-(1-pyrenylmethyl)glycerol] insertions on the structure and biological activity of a G-quadruplex from a critical KRAS G-rich sequence.
Quadruplex-forming oligonucleotides containing INA [(R)-1-O-(1-pyrenylmethyl)glycerol] insertions have been designed and studied for their capacity to inhibit the expression of the KRAS oncogene in pancreatic adenocarcinoma cells. It is found that INA can influence the folding topology of the G-quadruplex. The oligonucleotides forming the most stable G-quadruplex (ODN-637) is found to exhibit the highest bioactivity.
Cogoi
Susanna
S
Department of Biomedical Science and Technology, University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy.
Paramasivan
Manikandan
M
Xodo
L E
LE
Filichev
Vyacheslav V
VV
Pedersen
Erik B
EB
D001483:Base Sequence; D045744:Cell Line, Tumor; D054856:G-Quadruplexes; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011721:Pyrenes / Q000737:chemistry*; D014158:Transcription, Genetic / Q000187:drug effects*; D018631:ras Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
C527206:INA((R)-1-O-(1-pyrenylmethyl)glycerol); C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011721:Pyrenes; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D005990:Glycerol