Ivan Rosenberg

The Group´s principal interest consists in the synthesis and the biological and physico-chemical evaluation of novel, structurally diverse nucleoside phosphonic acids and corresponding phosphonate oligonucleotides containing isopolar P-C bridging internucleotide linkages. The main goals that we pursue, in general, are in bringing a new quality into the area of nucleoside/nucleotide antimetabolites, oligonucleotides interfering with gene expression, and those influencing natural cellular defence mechanisms.

More specifically, our research is aimed at the synthesis of (i) nucleoside phosphonic acids with respect to their potential inhibition of important enzymes of the metabolism of nucleotides and nucleosides, (ii) chimeric phosphonate oligonucleotides in the ribo and deoxyribo series to evaluate the nuclease resistance, hybridization properties, ability to elicit RNase H activity, cellular uptake, etc., and (iii) oligodeoxynucleotides with CpG motifs and short 5´-phosphorylated 2´-5´ oligoadenylates containing isopolar phosphonate linkages as potential agonists/antagonists of TLR9 and ribonuclease L, resp.

Structural properties of our compounds and their interactions at the molecular level are currently studied in collaboration with partners from inside and outside the Institute. NMR and Raman spectroscopy, surface plasmon resonance, differential scanning microcalorimetry, and MDS and ab initio calculations are currently exploited to understand more clearly the role of nucleotide and oligonucleotide-related structural factors that control interactions with biological targets.