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HomeHealthUnlocking Non-Canonical Amino Acids: Innovations in Photobiocatalysis for Peptide Therapeutics and Bioactive...

Unlocking Non-Canonical Amino Acids: Innovations in Photobiocatalysis for Peptide Therapeutics and Bioactive Products

UC Santa Barbara researchers are expanding the range of chemical reactions by utilizing light. They have developed a method using photobiocatalysis to create non-canonical amino acids, which are valuable components of peptide therapeutics, bioactive natural products, and innovative functional proteins. This achievement was reported in a paper published in the journal Nature by chemistry professor Yang Yang and collaborators at the University of Pittsburgh.naturally occurring) amino acids that are important for creating peptide therapeutics, bioactive natural products, and innovative functional proteins.

“There have been numerous advancements in the biocatalysis field, and we have reached a stage where we can intelligently create completely new enzymatic reactions that are unprecedented in both chemistry and biology,” stated Yang.

Most efforts in biocatalysis, which involves speeding up chemical reactions using enzymes, nature’s preferred catalysts, have focused on improving the functions of natural enzymes that are beneficial to synthetic chemistry, or adapting them for new and innovative purposes.Natural enzymes are utilized to aid in chemical reactions that are not typically found in nature. Despite years of research, there are only a few instances of enzymatic reactions that are new to both nature and synthetic chemistry. The goal is to discover entirely new enzymatic reactions and general enzyme catalysis modes.

Photobiocatalysis is a new field of chemistry that uses light to excite enzymes, producing energy (usually in the form of free radicals) to transform one molecule into another. This method takes advantage of the selective and efficient nature of enzymes.The study explores the merging of enzymes with the use of light to create new processes, specifically focusing on non-canonical amino acids.

Combining catalytic processes

The research team concentrated on pyridoxal-phosphate (PLP)-dependent enzymes, which play a key role in amino acid metabolism. They developed an interacting triple catalytic cycle involving a photocatalyst – an iridium-based compound – that reacts to light, producing a transient free radical. A second cycle using light then regenerates the photocatalyst.

CThe biocatalysis cycle using a PLP enzyme currently modifies the amino acid substrate through a series of unique activation steps specific to PLP biochemistry. The free radical produced from photochemistry plays a role in this process by entering the enzyme active site and interacting with the enzymatic intermediate to facilitate new chemistry. This collaboration between the enzyme and the photocatalyst enables the production of non-canonical amino acid products.

By altering the molecular structures of common amino acids, new features and capabilities are added to these acids. One example is the creation of a new carbon-carbon bond to the important “alpha carbon” of the amino acid.Yang stated that using this “backbone” opens up the possibility of creating a variety of new amino acids that could perform unique and desirable functions as the foundation for new therapeutics and natural products. Yang emphasized that this is the first demonstration of pyridoxical biocatalysis through radical-mediated alpha functionalization of abundant amino acid substrates.

Moreover, the process is highly efficient and stereoselective, meaning it can choose a preferred three-dimensional “shape” for the resulting amino acid, while also eliminating the need for additional steps of adding and removing “protecting groups” to mask certain compounds.active regions on molecules to prevent undesired chemical reactions in those regions.”We’ve discovered interesting interactions between the photocatalyst and the enzyme,” said Yang, whose team is investigating ways to enhance the interactions between the two catalysts. “I believe this will lead to new fundamental science, both in terms of synthetic chemistry and enzymology.”