Allosteric lariat peptide inhibitors of Abl kinase

Chembiochem. 2013 Nov 4;14(16):2119-25. doi: 10.1002/cbic.201300253. Epub 2013 Sep 12.

Abstract

Going against tradition: although most kinase inhibitors are ATP competitive, lariat peptides inhibit Abl kinase activity in an ATP-uncompetitive manner. Further, lariat peptides discriminated Src family kinases, and recognize the allosteric region that lies adjacent to the ATP binding pocket in the Abl kinase catalytic cleft.

Keywords: Abl kinase; combinatorial chemistry; enzyme inhibitors; lariat peptides; uncompetitive inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Allosteric Regulation
  • Amino Acid Sequence
  • Binding Sites
  • Catalytic Domain
  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • Humans
  • Kinetics
  • Peptides / chemistry
  • Peptides / metabolism*
  • Peptides / pharmacology*
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-abl / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-abl / metabolism

Substances

  • Peptides
  • Protein Kinase Inhibitors
  • Adenosine Triphosphate
  • Proto-Oncogene Proteins c-abl