Identification and Optimization of Protein Tyrosine Phosphatase Inhibitors Via Fragment Ligation

Abstract

Phosphotyrosine biomimetics are starting points for potent inhibitors of protein tyrosine phosphatases (PTPs) and, thus, crucial for drug development. Their identification, however, has been heavily driven by rational design, limiting the discovery of diverse, novel, and improved mimetics. In this chapter, we describe two screening approaches utilizing fragment ligation methods: one to identify new mimetics and the other to optimize existing mimetics into more potent and selective inhibitors.

Keywords: Fragment ligation; Fragment-based drug discovery; PTP; Phosphotyrosine mimetics; Protein tyrosine phosphatases; Screening.