Synthesizing Polymers Instead of Proteins Using Cellular Materials
Synthesizing Polymers Instead of Proteins Using Cellular Materials
  • Reporter Lee Ji-Hwan
  • 승인 2023.03.01 21:13
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▲Members of Prof. Lee Joongoo's lab.
▲Members of Prof. Lee Joongoo's lab.

Small-molecule drugs such as painkillers or digestive drugs are synthesized using chemical reactions. It is known that these small synthetic drugs need a drug-effective part called pharmacophore. However, introducing a pharmacophore into the drug molecule is limited because the overall synthetic procedures are complicated.
Professor Lee Joongoo's research team ( of the Department of Chemical Engineering (CE) conducted a joint study with Northwestern University and the University of Texas. The research team revealed a new fact that pharmacophores can be synthesized outside of cells through biochemical reactions used in the protein translation process. These findings were published in Nature Communications. (Title: Ribosome-mediated biosynthesis of pyridazinone oligomers in vitro)
Ribosome is a large molecule that has evolved within cells for billions of years. It is a polymerization machine that produces proteins by recognizing L-alpha-amino acids based on the genetic information transferred from mRNAs. Recently in synthetic biology, artificial amino acids that do not exist in nature have been extensively studied to produce novel bio-based materials as they can change biochemical properties when incorporated into natural proteins.
Through this study, the research team confirmed that when gamma-keto and hydrazino ester are continuously introduced into the ribosome, a 6-membered ring structure called “pyridazinone” is formed. The research team says that their approach can efficiently produce a wide variety of these ring structures. They further confirmed that the pyridazinone pharmacophores are consecutively introduced, forming a new backbone of a polymer.
In other words, if amino acids are polymerized in the ribosome, the monomers are linked together with a ‘handshake’ bond (peptide bond). But this study revealed that the monomers are connected with a “two-armed" bond, which is very difficult to implement with the current chemical approaches.
Prof. Lee, leading the study said “Molecular function of biochemicals evolved for a long time in cells are highly conserved in general, and their biological functions had evolved to work a specific biochemical reaction. Our result suggests that the various biochemical molecules used in protein translation are, in fact, not designed for a particular function and are actually versatile toward many other jobs, adding that, “We expect this cell-free system to develop a new drug synthesis platform producing many other pharmacophores and precision polymers.”