Synthesis, physicochemical and biochemical studies of anti-IRS-1 oligonucleotides containing carborane and/or metallacarborane modification

•DNA modified simultaneously with carborane and metallacarborane complex are described.•Physicochemical and biochemical properties of these modifications have been studied.•Antisense activity against IRS-1 gene was tested.

Modified oligonucleotides are potential candidates for therapeutic nucleic acids technology and applications as tools in molecular biology. Despite broad use and extensive studies of the modified DNA/RNA-oligomers there is a continuous need to improve their properties. These properties, related mainly to migration through the cell membranes, resistance to nucleolytic digestion and specific interaction with target sequence, can be improved by chemical modifications of the oligonucleotide backbone. In this study, we synthesized for the first time DNA-oligomers modified simultaneously with both, carborane and metallacarborane boron clusters and examined the physicochemical and biological properties of these bioorganic-inorganic constructs. The ability to silence the insulin receptor substrate 1 (IRS-1) gene overexpressed in several types of tumors by selected oligomers was tested in preliminary experiments. The lipophilicity and resistance to enzymatic degradation of the modified oligomers was higher than the unmodified counterparts. Effective formation of duplexes with complementary sequences was demonstrated, though antisense activity was not observed.

Graphical abstractDNA-oligomers modified simultaneously with both, carborane and metallacarborane boron clusters have been synthesized for the first time. The antisense activity of these bioorganic-inorganic constructs and ability to silence the insulin receptor substrate 1 (IRS-1) gene overexpressed in several types of tumors was tested in preliminary experiments.Figure optionsDownload full-size imageDownload as PowerPoint slide