Loading patent…
AssigneeAgouron Pharmaceuticals, Inc.
InventorsMichele A. McTigue, Chris Pinko, Camran V. Parast, Michael R. Gehring, Chen-Chen Kan, Krzysztof Appelt, John A. Wickersham, Richard E. Showalter, Anna M. Tempcyzk-Russell, Barbara Mroczkowski, Jesus E. Villafranca
Estimating the term…
A 2.4 Å crystal structure of a protein construct containing the catalytic kinase domain of vascular endothelial growth factor receptor 2 (VEGFR2/KDR), a key enzyme in angiogenesis, has been determined in an unliganded, phosphorylated state. This protein construct, contains a modified catalytic linker and has comparable in vitro kinase activity to constructs containing the entire KID. The resulting construct retains comparable in vitro kinase activity to that of the wild-type KID, and more importantly, allows complete crystallization of the protein such that it may be characterized by X-ray crystallography. The present invention further discloses the use of x-ray crystallographic data for identification and construction of possible therapeutic compounds in the treatment of various disease conditions.
A method for assaying a candidate compound for its ability to interact with a modified vascular endothelial growth factor receptor-2 (VEGFR-2) receptor polypeptide comprising:
An isolated DNA sequence or variants thereof encoding a modified vascular endothelial growth factor receptor-2 (VEGFR-2) gene construct wherein said VEGFR-2 gene contains a synthetic catalytic linker between helices αD and αE, wherein said linker comprises at least one amino acid from the kinase insert domain of the VEGFR-2 gene catalytic region.
Dependencies are inferred from the claim text.