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Taking chemical DNA-synthesis into flow – providing rapid access to modified oligonucleotides

PhD defence, Friday, 25 September 2020, Alexander Sandahl

2020.09.25 | Mie Meulengracht Christensen

Alexander Frederik Sandahl

Automated chemical synthesis of oligonucleotides is of fundamental importance for the production of primers for the polymerase chain reaction, for oligonucleotide-based drugs and for a numerous other medical and biotechnological applications. The highly optimized automized chemical oligonucleotide synthesis relies upon phosphoramidites as the phosphate precursors and one of the drawbacks of this technology is the poor bench stability of phosphoramidites. The technology saw its final developments in the late 1980s and the core methodology has remained unchanged since then.

During the PhD-study of Alexander Sandahl a flow-based method was developed for synthesis of phosphoramidites, which is accomplished with short reaction times, quantitative yields and without the need of purification before being submitted directly to automated oligonucleotide synthesis. Sterically hindered as well as redox unstable phosphoramidites have been synthesized using this methodology and the subsequent couplings are near quantitative for most substrates. The vision for this novel technology would be direct integration into DNA synthesizers thereby omitting manual synthesis and storage of phosphoramidites.

This project will be presented during the defense along with other projects related to solid-phase chemistry

The PhD degree was completed at the Interdisciplinary Nanoscience Center (iNANO), Faculty of Natural Sciences, Aarhus University.

This summary was prepared by the PhD student.

Time: Friday, 25 September 2020 at 13:15
Place: Due to Covid-19 only a limited audience is to attend the PhD defence at iNANO, if you wish to receive a link to the online version, please contact Ole Aalund Mandrup, oam@inano.au.dk  

Title of dissertation: Method Developments in Solid-Phase Chemistry: Easing Access to Synthetic Oligonucleotides and Oligo(disulfides)
Contact information: Alexander Sandahl, e-mail: Asandahl@inano.au.dk, tel.: +45 2567 4905
Members of the assessment committee:
Professor Thomas Carell, Fakultät für Chemie und Pharmazie, Ludwig-Maximilians-Universität München, Germany
Professor Jesper Wengel, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Denmark
Associate Professor Frans Mulder, iNANO and Department of Chemistry, Aarhus University (Chair)
Main supervisor: Professor Kurt V. Gothelf, iNANO and Department of Chemistry, Aarhus University

Language: The PhD dissertation will be defended in English
The defence is public.

Due to the coronavirus situation, the PhD thesis will not be available for reading at the offices of the PhD administration. Instead, interested parties may send an e-mail to gradschool.nat@au.dk to receive a digital copy of the PhD thesis. Please note, it may in certain cases be necessary to make an individual arrangement to read the PhD thesis.

PhD defence
16882 / i43