Chemical approaches to reversible protein phosphorylation.
Protein phosphorylation catalyzed by protein kinases plays a critical role in cellular signaling. Here we review several chemical approaches to understanding protein kinases and the consequences of protein phosphorylation. We discuss the design of bisubstrate analogue inhibitors based on a dissociative transition state, the development of reagents for cross-linking protein kinases with their substrates, the chemical rescue of mutant protein tyrosine kinases, and the application of expressed protein ligation to understanding protein phosphorylation.
Cole
Philip A
PA
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA. pcole@jhmi.edu
Courtney
Aliya D
AD
Shen
Kui
K
Zhang
Zhongsen
Z
Qiao
Yingfeng
Y
Lu
Wei
W
Williams
Daniel M
DM
D000595:Amino Acid Sequence; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D011506:Proteins; D011494:Protein Kinases