Delivering Mechanistic Understanding and Novel Approaches to Native Chemical Ligation

Native chemical ligation (NCL) is a chemical reaction which is critical in the synthesis of proteins. It has enabled chemists to prepare highly potent peptide-based pharmaceuticals for a range of diseases. Despite its ubiquity, aspects of the reaction's mechanism are still debated, so brute-force reaction screening is commonly employed, which is an expensive and time-consuming process. We will use a quantitative, combined synthetic-kinetic approach to elucidate the mechanism for NCL across a range of amino acids. Using this insight, we aim to understand current limitations and drawbacks of NCL in order to deliver better and more efficient synthetic procedures.