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Mechanism-Based Inhibitors of Alkyltransferases

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Biological Methylation and Drug Design

Part of the book series: Experimental Biology and Medicine ((EBAM,volume 12))

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Abstract

Alkyltransferases catalyze the reaction of various cellular nucleophiles with an electrophilic carbon adjacent to electron-deficient trivalent sulfur. In the case of methyltransferases, nucleophilic attack is at the methyl group of S-adenosylmethionine (AdoMet), whereas with the aminopropyltransferases, attack is at the less reactive aminopropyl methylene group of S-adenosyl(3-methylthio)-propylamine (decarboxylated AdoMet, dcAdoMet). Although nucleophilic attack at sp3 carbon is one of the most extensively studied reactions in organic chemistry, much less is known about the corresponding biochemical reactions catalyzed by the alkyltransferases. Our own mechanistic studies have focused on three areas of investigation: catalysis of non-enzymatic model reactions, kinetics of enzyme-catalyzed reactions, and stereochemistry of enzyme-catalyzed reactions. Since this research is the basis for our inhibitor design and synthesis work, it will be reveiwed briefly here.

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Coward, J.K. (1986). Mechanism-Based Inhibitors of Alkyltransferases. In: Borchardt, R.T., Creveling, C.R., Ueland, P.M. (eds) Biological Methylation and Drug Design. Experimental Biology and Medicine, vol 12. Humana Press. https://doi.org/10.1007/978-1-4612-5012-8_36

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  • DOI: https://doi.org/10.1007/978-1-4612-5012-8_36

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-4612-9398-9

  • Online ISBN: 978-1-4612-5012-8

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