Laboratory of Nanoscale Biology, School of Engineering, EPFL, STI IBI-STI LBEN BM 5134 (Bâtiment BM), Station 17, CH-1015, Lausanne, Switzerland.
Laboratory of Photochemistry and Spectroscopy, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001, Heverlee, Belgium.
Angew Chem Int Ed Engl. 2017 May 2;56(19):5182-5200. doi: 10.1002/anie.201608625. Epub 2017 Apr 10.
Methyltransferases (MTases) form a large family of enzymes that methylate a diverse set of targets, ranging from the three major biopolymers to small molecules. Most of these MTases use the cofactor S-adenosyl-l-Methionine (AdoMet) as a methyl source. In recent years, there have been significant efforts toward the development of AdoMet analogues with the aim of transferring moieties other than simple methyl groups. Two major classes of AdoMet analogues currently exist: doubly-activated molecules and aziridine based molecules, each of which employs a different approach to achieve transalkylation rather than transmethylation. In this review, we discuss the various strategies for labelling and functionalizing biomolecules using AdoMet-dependent MTases and AdoMet analogues. We cover the synthetic routes to AdoMet analogues, their stability in biological environments and their application in transalkylation reactions. Finally, some perspectives are presented for the potential use of AdoMet analogues in biology research, (epi)genetics and nanotechnology.
甲基转移酶(MTases)形成了一个庞大的酶家族,可甲基化各种不同的靶标,从三种主要的生物聚合物到小分子。这些 MTases 大多使用辅助因子 S-腺苷甲硫氨酸(AdoMet)作为甲基供体。近年来,人们在开发 AdoMet 类似物方面做出了巨大努力,旨在转移除简单甲基以外的基团。目前存在两类主要的 AdoMet 类似物:双重激活分子和氮丙啶基分子,它们各自采用不同的方法来实现转烷基化而不是转甲基化。在这篇综述中,我们讨论了使用 AdoMet 依赖性 MTases 和 AdoMet 类似物对生物分子进行标记和功能化的各种策略。我们涵盖了 AdoMet 类似物的合成途径、它们在生物环境中的稳定性以及它们在转烷基化反应中的应用。最后,我们对 AdoMet 类似物在生物学研究、(表观)遗传学和纳米技术中的潜在用途提出了一些看法。