Patent ID: 6162613
Filing Date: 2000-12-19
Classification: C12N,G01N

Abstract:
A method for designing an inhibitor of a second serine/threonine protein kinase or a second tyrosine protein kinase comprising the steps of:(a) providing a first serine/threonine protein kinase or first tyrosine protein kinase having a known three-dimensional structure;(b) identifying amino acids in an ATP binding site of said first serine/threonine protein kinase or said first tyrosine protein kinase that forms close contacts with a compound know to bind to said ATP binding site;(c) employing protein alignment means to identify in a second serine/threonine protein kinase or a second tyrosine kinase one or more amino acids that align with, but differ in identity from, said close contact amino acids in said first serine/threonine protein kinase or said first tyrosine protein kinase;(d) altering an amino acid in the ATP binding site of said second serine/threonine protein kinase or said second tyrosine protein kinase identified in step (c) to produce a mutant second serine/threonine protein kinase or a mutant second tyrosine protein kinase;(e) determining that said compound binds with at least 10-fold greater affinity to said mutant second serine/threonine protein kinase or said mutant second tyrosine protein kinase than to said second serine/threonine protein kinase or said second tyrosine protein kinase, and(f) using molecular modeling means to determine how to modify said compound to design an inhibitor of said second serine/threonine protein kinase or said second tyrosine protein kinase, wherein said inhibitor binds to said second serine/threonine protein kinase or said second tyrosine kinase with at least 10-fold greater affinity than said compound binds to said second serine/threonine protein kinase or said second tyrosine kinase, respectively.