The immucillins: Design, synthesis and application of transition-state analogues

Gary B. Evans, Vern L. Schramm, Peter C. Tyler

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Transition-state analysis based on kinetic isotope effects and computational chemistry provides electrostatic potential maps to serve as blueprints for the design and chemical synthesis of transition-state analogues. The utility of these molecules is exemplified by potential clinical applications toward leukemia, autoimmune disorders, gout, solid tumors, bacterial quorum sensing and bacterial antibiotics. In some cases, transition-state analogues have chemical features that have allowed them to be repurposed for new indications, including potential antiviral use. Three compounds from this family have entered clinical trials. The transition-state analogues bind to their target proteins with high affinity and specificity. The physical and structural properties of binding teach valuable and often surprising lessons about the nature of tight-binding inhibitors.

Original languageEnglish (US)
Pages (from-to)3897-3909
Number of pages13
JournalCurrent Medicinal Chemistry
Volume22
Issue number34
StatePublished - 2015

Keywords

  • Deaminases
  • Iminoribitols
  • N-ribosyltransferases
  • Nucleoside analogues
  • Transition-state analogues
  • Transition-state theory

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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