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A research team at the University of Cologne has developed an artificial DNA base pair that works according to a new chemical principle. In contrast to natural bases, the novel artificial base pairs use halogen bonds that are enzymatically incorporated into DNA / publication in the ‘Journal of the American Chemical Society’
For the first time, researchers have succeeded in developing an artificial DNA base pair that is based on a different chemical force than natural genetic material. While the common natural DNA building blocks are held together by hydrogen bonds, the new base pair relies on halogen bonds as its central attraction force. These act like tiny, precisely aligned ‘docking sites’ between molecules. The study demonstrates for the first time that such alternative bonds also enable stable DNA structures. It was published under the title ‘Investigating Halogen Bonds as Pairing Force in an Artificial DNA Base Pair’ in the Journal of the American Chemical Society.
Over the past decades, numerous artificial base pairs have been developed that mimic or complement the principle of hydrogen bonding. “Our approach takes it a step further: we developed a completely newly designed artificial base pair that uses halogen bonds as an alternative attractive force,” says principal investigator Professor Dr Stephanie Kath-Schorr from the University of Cologne’s Institute of Organic Chemistry. To achieve this, the team designed special chemical building blocks containing a halogen atom – in this case, iodine. Using computer simulations, the researchers first calculated how these building blocks needed to be arranged optimally. They subsequently produced the molecules in the laboratory and investigated whether they formed the intended bonds. The experiments confirmed that the novel building blocks reliably recognize each other and form a stable pair.
Particularly noteworthy is that a naturally occurring enzyme accepts the artificial building blocks. DNA polymerases are enzymes that function as the cell’s ‘copying machines’, synthesizing new DNA strands. In the experiments, the researchers demonstrated that a DNA polymerase can incorporate the newly developed building blocks into a growing DNA strand. Thus, the artificial base pair functions not only in a test tube but also within a biological context.
“DNA does not rely exclusively on the known chemical principle,” says Kath-Schorr. “Our results expand the genetic alphabet and deepen our understanding of how flexible the molecule of life truly is.” In the long term, such additional DNA building blocks could open up new possibilities in synthetic biology, for example in the development of novel diagnostic and therapeutic approaches.
Press and Communications Team:
Jan Voelkel
+49 221 470 2356
j.voelkel@verw.uni-koeln.de
Press spokesperson: Dr Elisabeth Hoffmann – e.hoffmann@verw.uni-koeln.de
Professor Dr Stephanie Kath-Schorr
Department of Chemistry and Biochemistry
Institute of Organic Chemistry
+49 221 470 4375
skathsch@uni-koeln.de
https://pubs.acs.org/doi/10.1021/jacs.5c23044
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