Delivering Mechanistic Understanding and Novel Approaches to Native Chemical Ligation

天然化学结扎（NCL）是一种在蛋白质合成中起关键作用的化学反应。它使化学家能够为一系列疾病制备高效的肽类药物。尽管它无处不在，但反应机制的各个方面仍存在争议，因此通常采用暴力反应筛选，这是一个昂贵且耗时的过程。我们将使用定量的，结合合成动力学的方法来阐明NCL在一系列氨基酸中的机制。利用这一见解，我们的目标是了解NCL目前的局限性和缺点，以便提供更好、更有效的合成程序。

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.