Researchers have created an artificial DNA sequence that can mimic its biological counterpart, take on its functions and even successfully compete with it. The structure was designed by a Ludwig-Maximilians-Universitaet (LMU) chemist and the results were published today in Nature Chemistry.
The new paper builds on research published earlier this year. In the first, the LMU team developed a pattern of binding interaction that enable synthetic molecules to assemble into stable forms similar to the helical backbone of proteins. In the second study, they worked out the conditions needed to allow their synthetic helix to be attached to proteins during synthesis by ribosomes.
These advances allowed them to build a synthetic molecule that folds into a helical structure, mimicking the surface of the DNA double helix. The shape of this molecule can be altered by the attachment of various substituents, allowing the researchers to better imitate the shape of natural DNA including the location of negative charge, which can act as a decoy for two DNA-binding enzymes, including HIV integrase. Binding of HIV integrase to the decoy molecule inactivates it, thus blocking HIV’s ability to incorporate into cells.
When tested in the presence of the normal DNA substrate as well as the synthetic molecule—dubbed a ‘foldamer’ by the team—the enzymes bound more readily to the foldamer, demonstrating its potential to effectively block viral enzymes.
While the team focused the current study on enzymes that are capable of binding to DNA irrespective of its base sequence, it may also be possible to use this approach to develop DNA mimics that block the action of DNA-binding proteins whose functions depend on recognition of specific nucleotide sequences.
Image: These are representations of a B-DNA double helix and a single helical foldamer mimic. Image courtesy of Ivan Huc, LMU.