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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  1. Minkui Luo
    57 Luo
  2. Xiaochuan   Cai
    4 Cai