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Aminopropyltransferases: Mechanistic Studies and the Synthesis of Specific Inhibitors

  • James K. Coward
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 250)

Abstract

We have studied the mechanism of enzyme-catalyzed alkyl transfer reactions by a variety of methods including non-enzymic model reactions, steady-state kinetics, and stereochemistry. In this brief paper, the results of our earlier work on catechol O-methyltransferase (COMT, E.C. 2.1.1.6) and more recent work on putrescine aminopropyltransferase (PAPT, E.C. 2.5.1.16, sometimes referred to as spermidine synthase) will be reviewed. These investigations have resulted in the demonstration that each of these alkyltransferases catalyze a reaction which proceeds via a ternary complex involving the enzyme and both nucleophilic and electrophilic substrates. In addition, the demonstration of general base catalysis in related model reactions, provides chemical precedent for the involvement of this type of catalysis by basic residues of the enzyme. The mechanistic conclusions have allowed us to design and synthesize several mechanism-based inhibitors which exhibit great potency and specificity for individual alkyltransferases1.

Keywords

Ternary Complex Purine Nucleoside Polyamine Biosynthesis Sulfonium Salt Electrophilic Substrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • James K. Coward
    • 1
  1. 1.Departments of Chemistry and Medicinal ChemistryThe University of MichiganAnn ArborUSA

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