POLYPEPTIDES SUBSTRATES OF LRRK2 AND USES THEREOF

摘要

A method for identifying a compound expected to be useful in modulating, for example inhibiting, LRRK2 protein kinase activity, the method comprising the steps of (1) determining whether a test compound modulates, for example inhibits, the protein kinase activity of a LRRK2 polypeptide on a substrate polypeptide and (2) selecting a compound which modulates, for example inhibits, the said LRRK2 polypeptide protein kinase activity, wherein the substrate polypeptide comprises the sequence (W/F/R/K)(W/F/R/K)(R/K)(F/W/H/R)(Y/W/R)(S/T)(L-/V/I)(R/K)(R/K)(A/Y) or (W/ R)(X)(X)(F/Y/H/T)(Y/W/R)(T)(X)(R/T)(R)(X), where X represents any amino acid. Such a compound may be useful in treating Parkinson's Disease or Parkinsonism. The substrate polypeptide may consist or comprise the sequence RLGWWRFYTLRRARQGNTKQR.