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Fragment Based Identification of Phosphatase Inhibitors

  • Author(s): Baguley, Tyler Daniel
  • Advisor(s): Ellman, Jonathan A
  • et al.

Phosphatases are broadly introduced as an enzyme class with therapeutic implications in a variety of disease areas. A substrate-based fragment approach is used to identify novel phosphatase inhibitors of first Mycobacterium tuberculosis protein tyrosine phosphatase PtpA, for potential therapeutic implications in tuberculosis, then for striatal-enriched protein tyrosine phosphatase (STEP), which has therapeutic implications for Alzheimer's disease. Finally, benzopentathiepins and seleninic acids are investigated as redox-reversible inhibitors of STEP. Aditionally, a method for the asymmetric additions of Knochel-type benzyl zinc reagents to N-tert-butanesulfinyl aldimines is described.

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