Using Light to Build New Drugs: Synthesis of Cyclic Peptides by Photoredox Chemistry, Cecilia Kim, UG '23 (3950214)
The emergence of new diseases, the rise of drug resistance, and the continued prevalence of chronic conditions that remain difficult to treat, such as cancer and Alzheimer’s, create a growing need for new and effective drugs. One class of pharmaceutical compounds that are becoming popular are cyclic peptides, which are made up of amino acids, the building blocks of proteins, that are in a ring form. Their circular shape and special properties make them promising therapeutic agents as they have increased stability in the body, high selectivity for new and specific biological targets, and increased effectiveness. They are, however, difficult to synthesize as the step to cyclize them may be hindered by low reactivity of the two ends of the peptide chain that need to be connected to form a ring, improper conformation in space that places the reacting ends far apart from one another, and unwanted side reactions so that there is only a small amount of product that is made. This project from the Knowles group in the Chemistry department aims to address these challenges by generating highly reactive molecules called radicals using a method known as photoredox chemistry, which uses light to push reactions forward. By computationally modeling and experimentally creating peptides that undergo this type of reaction, we hope to develop a new way to facilitate a reaction that will be critical in expanding our access to building new drugs to improve human health.