Fabricating site-specific protein conjugates is important for the development of protein therapeutics and uniform constructs that can be used to study function. Chemical ligation is one way to modify proteins; another is to use peptide ligases — such as sortase A, or peptidyl asparaginyl ligases (PALs) — which offer the benefits of enzymatic catalysis. PALs have a much higher catalytic efficiency than that of sortase A; however, PAL-mediated ligation is reversible and therefore requires a large excess of one of the reactants to shift the equilibrium to form the desired product. In an effort to address this limitation, Xia et al. have now reported a method for making a PAL-mediated intermolecular ligation irreversible.

制造位点特异性蛋白质偶联物对于开发可用于研究功能的蛋白质疗法和统一结构非常重要。化学连接是修饰蛋白质的一种方法；另一种方法是使用肽连接酶——例如分选酶 A 或肽基天冬酰胺酰连接酶 (PAL)——它们具有酶催化的优势。PALs的催化效率远高于分选酶A；然而，PAL 介导的连接是可逆的，因此需要大量过量的一种反应物来改变平衡以形成所需的产物。为了解决这一局限性，Xia 等人。现在已经报道了一种使 PAL 介导的分子间连接不可逆的方法。