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.
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.
Hubbard
Caitlin E
CE
Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.
Barrios
Amy M
AM
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry*; D010649:Phenylalanine / Q000031:analogs & derivatives*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D010455:Peptides; D010649:Phenylalanine; D017027:Protein Tyrosine Phosphatases