Effect of G-rich sequences on the synthesis, purification, hybridization, cell uptake, and hemolytic activity of oligonucleotides

We designed G-rich oligonucleotides in which the position and length of the guanosine residues were modified and studied the effects of these contiguous guanosine residues on the synthesis, purification, hybridization, cell uptake, and hemolytic effect of oligonucleotides. Our results revealed that the hyperstructure formation of these oligonucleotides depended on the length and position of the guanosine residues and the flanking sequences. The phosphorothioate oligonucleotides formed much less hyperstructures than their phosphodiester counterpart. These hyperstructures were more stable towards nucleases, were taken up by cells efficiently, and showed pronounced polyanionic related side-effects. Abstract Several phosphodiester and phosphorothioate G-rich oligonucleotides were synthesized and evaluated in respect of their ability to form hyperstructures and their hybridization characteristics. Additionally, their cell uptake and hemolytic activity were studied.