Proteins in hydrogel
A hydrogel for storing proteins was created from modified DNA
Alexander Dubov, N+1
With the help of chemical modification of saccharides in the DNA molecule, a team of American chemists obtained hydrogels that allow them to store proteins in themselves without losing their functional properties. The results of the study are published in Angewandte Chemie.
Schematic structure of a hydrogel made of modified DNA molecules with encapsulated protein molecules. Figure from the press release TSRI Chemists Use Modified DNA Nucleotides to Create New Materials
Chemical modification of DNA molecules allows you to change their physicochemical properties, control their primary structure with this, and thus control the processes of transcription and replication. The main problem of modified DNA is that during replication (synthesis of a single copy of a molecule) and amplification (creation of a large number of copies of individual segments of a molecule), DNA molecules with a conventional structure, rather than a modified one, are formed. This problem was partially solved by modifying the structure of nitrogenous bases. However, since chemical modification occurs at the level of individual nucleotides, replication of modified molecules is often difficult in this case.
In their new work, American chemists proposed chemically modifying not nitrogenous bases, which are responsible for creating a complementary bond between two DNA strands, but deoxyribose, a saccharide that forms a polymer chain. Of the five carbon atoms that make up deoxyribose, four atoms are occupied: the first binds the nitrogenous base, and the third, fourth and fifth are involved in the formation of bonds with neighboring nucleotides. Therefore, in order for the basic properties of DNA not to change much, scientists attached an additional chemical group to the second carbon atom.
Before that, scientists had already managed to obtain DNA molecules modified in this way with fluoride and methoxy groups. In this work, the scientists tried to modify the saccharide by adding an azide, chloride, hydroxyl or amino group.
Drawings from an article in Angewandte Chemie
It turned out that using a polymerase chain reaction, which is carried out by a special type of DNA polymerase, DNA oligomers can be synthesized from each of these modified nucleosides. All of the synthesized DNA sites were sensitive to replication and amplification.
In addition, scientists were able to use nucleotides modified by the azide group to obtain multi-linked structures. Two types of elements with forward and reverse sequences can be obtained from nucleotides of this composition. According to the mechanisms of click chemistry, these elements can be combined into multi-connected three–dimensional polymer meshes with hydrogel properties - they can stretch and contract when environmental conditions change.
The scheme of obtaining a DNA microgel from oligonucleotides
It is characteristic that such a hydrogel can be reversibly formed and dissolved under physiological conditions. Since DNA can be effectively bound to proteins, scientists have proposed using such a structure to encapsulate proteins without losing their functionality.
In their work, the scientists tested the effectiveness of this approach by encapsulating a horseradish peroxidase molecule in a DNA hydrogel, the biochemical activity of which remained after release from the hydrogel. According to scientists, the proposed DNA-based hydrogels can be used to store and work with a large number of different proteins.
Click chemistry is a set of approaches to the synthesis of complex chemicals by bonding individual small elements together. Similar approaches are used not only for reactions with DNA molecules, but also for other polymeric substances. For example, thanks to this method, scientists were able to synthesize complex supramolecular structures. Such a mechanism makes it possible to obtain organic crystals for solar panels.
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