Researchers have made a key discovery for safer drug development and biological research, as illustrated above
Azide is a useful chemical group that has many applications in fields like materials science, chemistry, drug discovery, and biology. One of its key uses is in a reaction called the azide-alkyne click reaction, a widely recognized reaction that has enabled many innovations in biology. This reaction has also facilitated the study of various biological molecules, from small drugs to larger structures like proteins and DNA. Notably, in 2022, the Nobel Prize in Chemistry was awarded jointly to Carolyn R. Bertozzi (former UC Berkeley chemistry faculty), Morten Meldal and K. Barry Sharpless “for the development of click chemistry and bioorthogonal chemistry.”
However, until recently, scientists hadn’t found a natural enzyme that could create azides from “scratch.” This is an oversimplification, of course, because the process is really more about creating complex molecules from simpler ones. (This process is called “de novo synthesis.”) Still, this was a problem scientists wanted to solve because it limited the ability to produce azides under mild, physiological conditions – gentler conditions – that wouldn’t interfere with biological systems.
Why is that important? For many reasons, but as an example, if these azides can be created mildly, they can be used in living organisms without causing harm. This is obviously crucial for applications in drug development and biological research.
In a study published by Nature Chemistry, a team of UC Berkeley researchers at the College of Chemistry led by Wenjun Zhang, Ph.D., in collaboration with the Kulik group at MIT, reported the discovery of the first natural enzyme capable of creating these complex molecules–azides–from simpler ones. They identified an enzyme called Tri17 that uses ATP and nitrite to create different types of azides through a series of chemical reactions. By studying the structure and function of Tri17, scientists learned how it helps form azides.
This discovery opens up new possibilities for using biological processes to produce azides. It is exciting for a variety of reasons, mostly because it could lead to exciting advancements in synthetic biology and chemical research. This could include the development of medical advances that target diseases more effectively, the ability to better understand how our bodies work – leading to breakthroughs in treatments – and the development of new materials.
Read the full paper published by Nature Chemistry .