Patent ID: 7584087
Filing Date: 2009-09-01
Classification: A61P,C07K,C12N,C12Q,G01N

Abstract:
1. A method of designing a candidate agent that interacts with protein kinase C theta (PKCθ), comprising: (a) generating a three-dimensional model of the catalytic domain of PKCθ defined by the three-dimensional structural coordinates of the complex of the catalytic domain of PKCθ and staurosporine according to Table 2, ± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å, wherein the catalytic domain of PKCθ of the complex according to Table 2 consists of amino acids Ile377 to Pro649 and Gln688 to Phe696 of SEQ ID NO: 1; (b) identifying the amino acid residues forming the ATP-binding pocket of the catalytic domain of PKCθ from the three-dimensional model in step (a) in order to generate a three-dimensional representation of the ATP-binding pocket which comprises the structural coordinates of residues Leu386, Gly387, Gly389, Val394, Ala407, Lys409, Val422, Glu428, Met458, Glu459, Tyr460, Leu461, Gly464, Leu466, Arg503, Asp504, Asp508, Asn509, Leu511, Ala521, Asp522, Lys527, Thr536, and Thr538 according to Table 2± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å; (c) employing said three-dimensional representation from step (b) to design said candidate agent; (d) synthesizing said candidate agent; (e) contacting said candidate agent with said catalytic domain of PKCθ polypeptide; and (f) detecting the ability of the candidate agent to bind to the catalytic domain of the PKCθ polypeptide, whereby the detection of the ability of said candidate agent to interact or bind said catalytic domain of PKCθ polypeptide thereby identifies said candidate agent as an agent that interacts with PKCθ.