Cell-permeable bicyclic peptidyl inhibitors against T-cell protein tyrosine phosphatase from a combinatorial library

Org Biomol Chem. 2017 Nov 22;15(45):9595-9598. doi: 10.1039/c7ob02562a.

Abstract

Protein tyrosine phosphatases (PTPs) have been challenging targets for inhibitor design, because all PTPs share a highly conserved active site structure, which is positively charged and requires negatively charged moieties for tight binding. In this study, we developed cell-permeable bicyclic peptidyl inhibitors against T-cell PTP (TCPTP), which feature a cell-penetrating motif in one ring and a target-binding sequence in the second ring.

MeSH terms

  • Combinatorial Chemistry Techniques*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • HeLa Cells
  • Humans
  • Molecular Conformation
  • Peptide Library
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / metabolism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Peptide Library
  • Peptides, Cyclic
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2