61925-80-2Relevant academic research and scientific papers
Synthesis and evaluation of multisubstrate inhibitors of an oncogene-encoded tyrosine-specific protein kinase. 2
Kruse,Holden,Offen,Pritchard,Feild,Rieman,Bender,Ferguson,Greig,Poste
, p. 1768 - 1772 (2007/10/02)
Tyrosine-specific protein kinases that transfer the terminal phosphate from ATP to protein acceptors are associated with certain transforming viruses and cell surface growth factor receptors. Here we describe the synthesis and testing of potential multisubstrate inhibitors of this class of enzymes. The inhibitors were prepared by covalent attachment of the terminal phosphate of ATP or its tetraphosphate analogue to tyrosine mimics. Testing against p60(v-abl), the tyrosine kinase from the Abelson murine leukemia virus, showed that the series of inhibitors was moderately potent (IV50 values as low as 13 μM). However, structural modification of the tyrosine mimic, including replacement with a serine-like moiety, had little effect on potency. It is therefore concluded that the ATP moiety is largely responsible for binding and that the enzyme requires additional structural features for recognition of the tyrosine-containing substrate.
