UNIST chemistry professor Park Chul-min’s team has developed a chemical catalyst-based transformation technology that can attach a functional group to a specific location of DNA or RNA fragments, the “oligonucleotide”.
The site-selective modification of oligonucleotide provides indispensable research tools in research fields such as basic life phenomena research, new drug development, and nanotechnology. The currently standardized method of obtaining modified oligonucleotide is the solid-phase oligonucleotide synthesis. Pre-functionalized nucleoside phosphoramidite monomolecules (pre-functionalized) are the raw materials. However, this method takes a long time to synthesize raw materials, and because of the post-processing process, it is difficult to introduce agents that are vulnerable to acids or bases. For this reason, more efficient post-synthetic variants have been developed. There are methods to use enzymes, biological catalysts, and SELEX. However, there are problems that are mostly time and cost burdens.
The research team developed a chemical modification method that transforms oligonucleotide with a Rhodium metal-based carbine catalyst (Rh(I)-carbene). This method can cause a reaction at a particular location. It has the advantage of saving money and time over the biological method of using enzymes in chemical ways that are chemical.
In addition, unlike conventional copper-based chemical catalysts, they overcome the problem of low efficiency (transition, turnover) of conventional chemical catalysts because they are challation-free catalysts.
The team demonstrated this through the Density function theory. It was revealed that the rhodium (I) carbine complex produced within the reaction immediately reacts to the O6 position of guanosine without any killation.
The team developed a location-selective response through the formation of guanosine (G) bulge structures, based on the difference in reactivity between guanosine and non-guanosine, which form a base pairs.
The above response is applicable to all different substrates with complex and diverse secondary structures and has the advantage of being able to selectively obtain products at high yields in a short time.
Through the method developed, the team was able to selectively introduce various actuators by changing the single strand oligonucleotide and the opposite strand. The developed method allows the introduction of chemical ligation of oligonucleotides, which can reduce costs by not using enzymes, and photocaging groups that can be easily removed using light. The use of modified oligonucleotides also reduces binding force, making it easier to detect DNA-binding proteins, which are essential for refining and analysis.
This study allowed for location-selective oligonucleotide deformation in a short time without long and expensive enzymes or complex processes. The modification method of this study is expected to contribute to the development of various fields such as research of life phenomena, development of new drugs, and nanotechnology by providing a method of introducing an agonist at the desired location of oligonucleotides.
Image: DNA-Binding Protein (Image source: https://images.app.goo.gl/AsKMTiD8bHerE6dQ7)