It is the purpose of the project to study the synthesis and
physicochemical properties of new antisense oligonucleotides. Recently new oligomers (HNA) containing anhydrohexitol building blocks have been discovered in the host laboratory as being the strongest hybridising antisense constructs (with natural DNA and RNA) found till now. During this project the fundamental studies will be carried out which are necessary to investigate the potential of these constructs for further development (as anticancer and antiviral therapeutics).
First we will study the kinetics of association of HNA oligomers with natural DNA and RNA. Secondly, we will incorporate base modification (5-methylcytosine, 7-deaza-guanine) with the aim of selecting the best base-pairing system with lack of toxicity. Applications in the cancer field (anti-ras oligomer) will be considered at the end of the project.