Paper co-authored by Patrick Willoughby published in Nature Chemistry journal

Associate Professor of Chemistry Patrick H. Willoughby co-authored a paper published in Nature Chemistry, the chemistry-focused subsidiary journal of Nature.

The paper, “Biocatalytic asymmetric aldol addition into unactivated ketones,” describes new approaches for the enzyme-catalyzed synthesis of amino acids. Willoughby worked alongside his students and his collaborators at UW-Madison to expand this idea to include ketone substrates.

“The proteins in our bodies are made from 20 amino acid molecules,” Willoughby said. “My collaborators and I have been working to invent new amino acids that are variants of the natural 20. This paper describes new amino acids that are made by bonding to a ketone molecule, which greatly increases the diversity of products.”

Willoughby said some of the most important medical breakthroughs are from pharmaceuticals that include unnatural (or non-standard) amino acids.

“The amino acids reported in this study are entirely new to nature and represent new possibilities for developing the next generation of peptide therapeutics,” Willoughby said.

Willoughby’s work on the paper came in towards the end of the writing process when his collaborators utilized a technique he and his students discovered at Ripon College.

“In the fall of 2023, my students discovered that replacing the alanine component of our analysis with a proline molecule greatly increased the efficiency of the technique,” Willoughby said. “I shared this discovery with my collaborators who immediately used the updated technique to analyze some of the more challenging substrates.”

After the discovery, Willoughby delivered some material to Madison and provided consultation. He also contributed to preparing the manuscript during the revision process.

“In addition to inventing new amino acids, I have been working with the Buller group from UW-Madison to improve techniques used to determine the stereochemical purity of the newly made amino acids,” Willoughby said. “Stereochemical purity is essential for ensuring molecules can be safely incorporated in medicinal therapeutics.”

A comprehensive report is being developed with assistance from Willoughby’s students.

“Getting published is always exciting, and this is an excellent first step,” Willoughby said. “My students are currently finishing up the full report on the revised technique. After that report, we hope to publish a general protocol that reviews the evolution of the technique from its first discovery in 1984 to our recent contribution.”