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Content archived on 2022-12-23

Biologically important modified oligonucleotides with increased stability towards nucleases and phosphodiesterases

Objective



Among the eleven synthetic antiviral drugs licensed at this time, ten are nucleoside analogues. Several nucleoside and oligonucleotide (ON) analogues are undergoing clinical trials.

The artificial control of gene expression by modified ON provides an exciting opportunity for the rational design of antisens oligonucleotides having antiviral and antitumor activity and can be used for therapeutic purposes. It is known that ON are not readily taken up by the intact eucaryotic cell, and they are rapidly hydrolysed by phosphodiesterases and nucleases. Chemical modification of ON might provide solutions to these problems.

The project is a collaborative action for the synthesis of modified ribooligonucleotides of biological importance with improved stability towards cell enzymes. The scientific results of this collaboration have been published in 20 articles.

The main goal of this project is the synthesis of biologically active stable sugar modified 2',5'-oligoadenylates and ON derivatives with reactive groups. Such ON derivatives may be considered as potential selective inhibitors of viral DNA polymerases and reverse transcriptases.

The work to be carried out will be as follows: a preparation of novel nucleoside analogues; an investigation of nucleosides analogs Physico-Chemical and conformational properties; a preparation of different 2',5'-oligoadenylates; a stability of new ON derivative; a preparation of modified ON; a Physico-Chemical investigation of complex formation between modified ON and short DNA's; an investigation of antiviral properties; and the use of complex ON-DNA for an inhibition of DNA polymerases and reverse transcriptases.

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Programme(s)

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Topic(s)

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Call for proposal

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Funding Scheme

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Coordinator

Katholieke Universiteit Leuven
EU contribution
No data
Address
Minderbroedersstrat 10
3000 Leuven
Belgium

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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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Participants (4)

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