Objective
The aim of this project is the design of interactive antisense oligonucleotides for therapeutic use at physiological temperatures. This requires that the specificity of hybridisation be maintained and the thermal behaviour, i.e. the discriminatory temperature range near melting, adapted to physiological conditions.
As a route to achieving this goal, chimeric oligonucleotide-oligoethylene glycol oligoether-phosphates are prepared. In these chimeric compounds, the oligonucleotide segments will be short enough to ensure melting temperatures near physiological, whereas the total length of base pairing will be maintained around 17-20 bases to ensure maximum specificity. The oligoethylene glycol moieties will not only serve as spacers between the oligonucleotide segments, but may also enhance the cellular uptake of these macromolecules.
The conjugation to organic substituents will be studied as follows: modulate oligonucleotide hybridisation (e.g. phenazinium residues); account for improved uptake, and produce cytotoxic effects in target cells by, non-triggered interaction with nucleic acids through alkylating residues or by triggered cleavage of nucleic acids by hydrophilic porphine moieties.
Call for proposal
Data not availableFunding Scheme
Data not availableCoordinator
89069 Ulm
Germany