The immucillins

Design, synthesis and application of transition-state analogues

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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

Fingerprint

Computational chemistry
Blueprints
Quorum Sensing
Gout
Static Electricity
Isotopes
Antiviral Agents
Structural properties
Tumors
Electrostatics
Leukemia
Physical properties
Clinical Trials
Anti-Bacterial Agents
Molecules
Kinetics
Neoplasms
Proteins

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

The immucillins : Design, synthesis and application of transition-state analogues. / Evans, Gary B.; Schramm, Vern L.; Tyler, Peter C.

In: Current Medicinal Chemistry, Vol. 22, No. 34, 2015, p. 3897-3909.

Research output: Contribution to journalArticle

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