ISSN:
0006-3525
Keywords:
protein tyrosine kinases (PTK)
;
PTK structure
;
substrate specificity
;
drug discovery
;
cell regulation
;
substrate motifs
;
protein kinase assays
;
protein kinase inhibitors
;
Chemistry
;
Polymer and Materials Science
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Protein tyrosine kinases (PTKs) play a crucial role in many cell regulatory processes. It is therefore not surprising to see that functional perturbation of PTKs results in many diseases. Despite the diverse primary structure organization of various PTKs, the catalytic or kinase domains of various PTKs as well as that of Ser/Thr kinases are generally conserved. The high resolution crystal structure of a few PTKs has been solved in the last few years. In contrast to the well-defined linear peptide substrate motifs recognized by specific Ser/Thr kinases, the identification of specific substrate motifs for PTK has been slow. It is not until recently that through the use of combinatorial peptide library methods that specific recognition motifs for specific PTKs have begun to emerge. Efficient and specific peptide substrates for some PTKs with Km at the mid μM range have been identified. Based on these peptide substrates, relatively potent (IC50 at the low μM range) and highly selective pseudosubstrate-based peptide inhibitors have been developed. There has been enormous effort in the development of PTK inhibitors for diseases such as cancer, psoriasis, and osteoporosis. Several new high-throughput PTK assay technologies have recently been described. Small molecules against specific PTK have been developed. Most of them are competitive inhibitors at the ATP binding site. Some of these inhibitors have already been in clinical trial. © 1998 John Wiley & Sons, Inc. Biopoly 47: 197-223, 1998
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
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