Inhibition of a protein tyrosine phosphatase using mesoporous oxides

J Phys Chem B. 2010 Mar 11;114(9):3117-21. doi: 10.1021/jp910166h.

Abstract

The feasibility of utilizing mesoporous matrices of alumina and silica for the inhibition of enzymatic activity is presented here. These studies were performed on a protein tyrosine phosphatase by the name chick retinal tyrosine phosphotase-2 (CRYP-2), a protein that is identical in sequence to the human glomerular epithelial protein-1 and involved in hepatic carcinoma. The inhibition of CRYP-2 is of tremendous therapeutic importance. Inhibition of catalytic activity was examined using the sustained delivery of p-nitrocatechol sulfate (pNCS) from bare and amine functionalized mesoporous silica (MCM-48) and mesoporous alumina (Al(2)O(3)). Among the various mesoporous matrices employed, amine functionalized MCM-48 exhibited the best release of pNCS and also inhibition of CRYP-2. The maximum speed of reaction v(max) (=160 +/- 10 micromol/mnt/mg) and inhibition constant K(i) (=85.0 +/- 5.0 micromol) estimated using a competitive inhibition model were found to be very similar to inhibition activities of protein tyrosine phosphatases using other methods.

MeSH terms

  • Aluminum Oxide / chemistry
  • Aluminum Oxide / pharmacology
  • Animals
  • Chickens
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemistry*
  • Humans
  • Kinetics
  • Oxides / chemistry*
  • Porosity
  • Protein Structure, Tertiary
  • Protein Tyrosine Phosphatases / chemistry
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / chemistry
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Silicon Dioxide / chemistry
  • Silicon Dioxide / pharmacology

Substances

  • Enzyme Inhibitors
  • Oxides
  • Recombinant Proteins
  • Silicon Dioxide
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3
  • Aluminum Oxide