The ability to construct a peptide or protein in a spatio-specific manner is of great interest for therapeutic and biochemical research. However, the various functional groups present in peptide sequences and the need to perform chemistry under mild and aqueous conditions make selective protein functionalization one of the greatest synthetic challenges. The fascinating paradox of selenium (Se) — being found in both toxic compounds and also harnessed by nature for essential biochemical processes — has inspired the recent exploration of selenium chemistry for site-selective functionalization of peptides and proteins. In this Review, we discuss such approaches, including metal-free and metal-catalysed transformations, as well as traceless chemical modifications. We report their advantages, limitations and applications, as well as future research avenues.

以空间特异性方式构建肽或蛋白质的能力对于治疗和生化研究非常有意义。然而，肽序列中存在的各种官能团以及在温和和水性条件下进行化学反应的需要使得选择性蛋白质功能化成为最大的合成挑战之一。硒 (Se) 的迷人悖论——既存在于有毒化合物中，又被大自然用于重要的生化过程——激发了最近对硒化学对肽和蛋白质的位点选择性功能化的探索。在这篇综述中，我们讨论了这些方法，包括无金属和金属催化的转化，以及无痕化学修饰。我们报告它们的优点、局限性和应用，以及未来的研究途径。