4 years ago

Methyltransferase-Directed Labeling of Biomolecules and its Applications

Methyltransferase-Directed Labeling of Biomolecules and its Applications
Jochem Deen, Kris P. F. Janssen, Johan Hofkens, Volker Leen, Charlotte Vranken, Robert K. Neely
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. Enzymatic methylation by methyltransferases (MTases) is an important biological process, and most MTases use the cofactor S-adenosyl-l-Methionine (AdoMet) as a methyl source. This Review summarizes the use of AdoMet-dependent MTases and AdoMet analogues for the transalkylation of various biomolecules. Different AdoMet analogues and their application to the functionalization of DNA, RNA, and proteins will be discussed.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201608625

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