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Kinase Inhibition by Di-Nucleoside Phosphates

Protein kinases catalyze the phosphorylation of substrate proteins by transfer of the γ-phosphate of ATP to the acceptor amino acid. Therefore, they play a key role in cell signaling and regulate biological processes such as proliferation, differentiation, and apoptosis. The malfunctioning of these proteins is the root of many diseases.

Protein kinase inhibitors have been paid much attention in the recent years, especially, in drug discovery. There are basically five classes of kinase inhibitors:

  • ATP-site inhibitors
  • Peptide-site inhibitors
  • Bisubstrate inhibitors directed simultaneously at the ATP-site and the peptide-site
  • Regulatory domain targeting inhibitors
  • Docking site blocking inhibitors
The combination of structural elements of peptide-site and ATP-site inhibitors in one molecule renders bisubstate inhibitors particularly interesting for mechanistic studies on nucleotide kinases.

The general formula of Jena Bioscience's bisubstrate inhibitors is N-Pn-N' where P is a phosphate chain of the length n and N and N', respectively, are ribo- or deoxy-nucleotides.

For a review please see:
Guranowski (2003) Analogs of diadenosine tetraphosphate. Acta Biochimica Polonia 50:947.