Synthesis and assays of inhibitors of methyltransferases Journal Article
| Authors: | Cai, X. C.; Kapilashrami, K.; Luo, M. |
| Article Title: | Synthesis and assays of inhibitors of methyltransferases |
| Abstract: | Epigenetic regulation requires site-specific modification of the genome and is involved in multiple physiological processes and disease etiology. Methyltransferases, which catalyze the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to various substrates, are critical components of the epigenetic machinery. This group of enzymes can methylate diverse substrates including DNA, RNA, proteins, and small-molecule metabolites. Their dysregulation has also been implicated in multiple disease states such as cancer, neurological, and cardiovascular disorders. Developing potent and selective small-molecule inhibitors of methyltransferases is valuable not only for therapeutic intervention but also for investigating the roles of these enzymes in disease progression. In this chapter, we will discuss the strategies of designing and synthesizing methyltransferases inhibitors based on the SAM scaffold. Following the section of inhibitor design, we will briefly review representative assays that are available to evaluate the potency of these inhibitors along with a detailed description of the most commonly used radiometric assay. © 2016 Elsevier Inc. |
| Keywords: | methylation; animal; metabolism; animals; enzyme inhibitor; drug evaluation, preclinical; drug design; methyltransferase; chemistry; methyltransferases; enzyme inhibitors; epigenetics; enzyme assay; synthesis; inhibition; s-adenosyl-l-methionine; enzyme assays; procedures; sinefungin; preclinical study; chemistry techniques, synthetic; humans; human; antagonists and inhibitors; s-adenosyl-l-homocysteine; structure-based inhibitor design |
| Journal Title: | Methods in Enzymology |
| Volume: | 574 |
| ISSN: | 0076-6879 |
| Publisher: | Academic Press |
| Date Published: | 2016-01-01 |
| Start Page: | 245 |
| End Page: | 308 |
| Language: | English |
| DOI: | 10.1016/bs.mie.2016.01.009 |
| PUBMED: | 27423865 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Chapter: 11 in "Enzymes of Epigenetics, Part B" (ISBN: 978-0-12-805381-2) -- Export Date: 2 April 2018 -- Source: Scopus |
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