A highly efficient route to enantiomerically pure l-N-Bz-Pmp(t-Bu)2-OH and incorporation into a peptide-based protein tyrosine phosphatase inhibitor

Bioorg Med Chem Lett. 2008 Jan 15;18(2):679-81. doi: 10.1016/j.bmcl.2007.11.056.

Abstract

Phosphonomethyl phenylalanine (Pmp), a nonhydrolyzable mimic of phosphotyrosine, is an important building block in the development of peptide-based PTP inhibitors. We have designed a novel, efficient synthesis of N-Bz-Pmp(t-Bu)2-OH. A Pmp-containing peptide based on a known biological substrate of the tyrosine phosphatase CD45 (Ac-TEGQ-Pmp-QPQP-NH2) inhibits CD45 with an IC50 value of approximately 100 microM with virtually no inhibition of TCPTP up to concentrations of 120 microM.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Peptides / chemistry*
  • Phenylalanine / analogs & derivatives*
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Stereoisomerism

Substances

  • Enzyme Inhibitors
  • Peptides
  • Phenylalanine
  • Protein Tyrosine Phosphatases