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.