MilliporeSigma
  • Home
  • Search Results
  • Light-switched inhibitors of protein tyrosine phosphatase PTP1B based on phosphonocarbonyl phenylalanine as photoactive phosphotyrosine mimetic.

Light-switched inhibitors of protein tyrosine phosphatase PTP1B based on phosphonocarbonyl phenylalanine as photoactive phosphotyrosine mimetic.

Bioorganic & medicinal chemistry (2015-04-25)
Stefan Wagner, Anja Schütz, Jörg Rademann
ABSTRACT

Phosphopeptide mimetics containing the 4-phosphonocarbonyl phenylalanine (pcF) as a photo-active phosphotyrosine isoster are developed as potent, light-switchable inhibitors of the protein tyrosine phosphatase PTP1B. The photo-active inhibitors 6-10 are derived from phosphopeptide substrates and are prepared from the suitably protected pcF building block 12 by Fmoc-based solid phase peptide synthesis. All pcF-containing peptides are moderate inhibitors of PTP1B with KI values between 10 and 50μM. Irradiation of the inhibitors at 365nm in the presence of the protein PTP1B amplify the inhibitory activity of pcF-peptides up to 120-fold, switching the KI values of the best inhibitors to the sub-micromolar range. Photo-activation of the inhibitors results in the formation of triplet intermediates of the benzoylphosphonate moiety, which deactivate PTP1B following an oxidative radical mechanism. Deactivation of PTP1B proceeds without covalent crosslinking of the protein target with the photo-switched inhibitors and can be reverted by subsequent addition of reducing agent dithiothreitol (DTT).

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Water, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Water, deuterium-depleted, ≤1 ppm (Deuterium oxide)
Sigma-Aldrich
Water, for embryo transfer, sterile-filtered, BioXtra, suitable for mouse embryo cell culture
Sigma-Aldrich
E-Toxate Water, endotoxin, free
Sigma-Aldrich
Water, Nuclease-Free Water, for Molecular Biology
Sigma-Aldrich
Water, for cell biology, sterile ultrafiltered
Sigma-Aldrich
Water, for molecular biology, sterile filtered
Sigma-Aldrich
Water, PCR Reagent
Sigma-Aldrich
Water, BioPerformance Certified
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Water-16O, ≥99.94 atom % 16O
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications