Chemistry of Nucleosides and Nucleotides
Our laboratory is part of the Nucleotides and Oligonucleotides group at the Institute of Organic Chemistry and Biochemistry AV CR; our topics are connected to this group. The leitmotif of our work is the synthesis of nucleoside phosphonic acids. These types of compounds have repeatedly demonstrated their qualities—the acyclic derivatives of nucleoside phosphonic acids are the active ingredient of drugs against HIV and other dangerous viruses; bisphosphonates are part of drugs against osteoporosis.
At the forefront of our interests are oligonucleotides in which phosphate linkages between nucleotide units are replaced by a bond phosphonate. This substitution of the ester bond of P-O to the enzymatically non-cleavable bond P-C provides greater stability of the oligonucleotide molecules in cells and thereby increases their potential biological effect. Preparation of the oligonucleotide takes place on a solid phase using an automatic synthesizer.
During the preparation of monomers for automated solid phase synthesis, we prepare a number of structurally diverse nucleoside derivatives which, in cooperation with other departments, we test for their possible biological effects both in vitro (enzyme assay) and in vivo (cells and cell lines assay).
Our prepared modified nucleotides can affect DNA replication (grow the merging chain termination DNA) and oligonucleotides consisting of the nucleotide analogues may, for example, suppress gene expression (steric block mechanism, RNase H) and affect gene silencing (siRNA). Nucleoside phosphonic acids may also act as inhibitors of various important enzymes (thymidine phosphorylase, nucleotidases) to influence events in healthy and diseased cells.
For students, we offer participation in a friendly and helpful scientific team with considerable experience in the chemistry of nucleosides, nucleotides and oligonucleotides, and all the modern facilities of the IOCB AS CR.