C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/19 (2006.01) A61K 38/19 (2006.01) A61P 37/02 (2006.01) C07K 14/52 (2006.01) C07K 16/24 (2006.01) C07K 19/00 (2006.01) C12Q 1/02 (2006.01) G01N 33/566 (2006.01)
Patent
CA 2466877
The inventors have discovered that a CK.beta.8-1 truncation variant, CK.beta.8- 1 (25-116), is a bifunctional ligand for two distinct GPCRs, chemokine receptor CCR1 and formyl peptide receptor like 1 (FPRL1). Hence, the inventors have discovered that, in addition to its functional activity on CCR1, CK.beta.8-1(25-116) is also a functional ligand for the GPCR receptor FPRL1 that is involved in inflammatory reactions and innate immunity by recruiting monocytes and neutrophils. In addition, the inventors have discovered an alternatively spliced exon of CK.beta.8-1, named SHAAGtide. SHAAGtide, along with its parent chemokine CK.beta.8-1(25-116), is fully functional on both monocytes and neutrophils that are known to express FPRL1.
L'invention concerne la découverte selon laquelle une variante de troncature de CK.beta.8-1, CK.beta.8-1 (25-116), constitue un ligand bifonctionnel pour deux GPCR distincts, le récepteur des chimiokines CCR1 et le récepteur de type récepteur 1 des peptides formylés (FPRL1). Outre son activité fonctionnelle par rapport à CCR1, CK.beta.8-1(25-116) constitue aussi un ligand fonctionnel du récepteur GPCR FPRL1, qui intervient dans les réactions inflammatoires et l'immunité naturelle en recrutant monocytes et neutrophiles. L'invention concerne de plus un exon obtenu par l'épissage alternatif de CK.beta.8-1, appelé SHAAGtide. SHAAGtide, ainsi que la chimiokine parent CK.beta.8-1(25-116), est entièrement fonctionnel à l'égard des monocytes et des neutrophiles, qui sont connus pour exprimer FPRL1.
Miao Zhenhua
Premack Brett
Schall Thomas J.
Cassan Maclean
Chemocentryx Inc.
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