C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 16/40 (2006.01) C07K 7/06 (2006.01) C07K 14/00 (2006.01) C12N 15/00 (2006.01) C12Q 1/48 (2006.01) G01N 33/50 (2006.01) G01N 33/68 (2006.01) C12N 15/54 (2006.01)
Patent
CA 2737507
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.
L'invention concerne un procédé d'identification d'un composé susceptible d'être utile pour moduler, par exemple inhiber, l'activité protéine kinase de LRRK2, le procédé comprenant les étapes consistant à (1) déterminer si un composé testé module, par exemple inhibe, l'activité protéine kinase d'un polypeptide LRRK2, sur un polypeptide substrat et (2) sélectionner un composé qui module, par exemple inhibe, ladite activité protéine kinase d'un polypeptide LRRK2, ledit polypeptide substrat comprenant la séquence (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) ou (W/ R)(X)(X)(F/Y/H/T)(Y/W/R)(T)(X)(R/T)(R)(X), dans lesquelles X représente un acide aminé quelconque. Un tel composé peut être utile dans le traitement de la maladie de Parkinson ou du syndrome parkinsonien. Le polypeptide substrat peut consister en la séquence RLGWWRFYTLRRARQGNTKQR ou comprendre cette séquence.
Alessi Dario
Nichols Jeremy R.
Bereskin & Parr Llp/s.e.n.c.r.l.,s.r.l.
Medical Research Council
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