title: Selective inhibition of tyrosine protein kinase by a synthetic multisubstrate analog.
abstract: Synthetic compounds were designed in an attempt to mimic the possible transition state of tyrosine protein kinases. One representative compound (RP 53801) inhibited the enzyme purified from RSV-transformed cells. A serine/threonine kinase (kinase C) was 45 fold less sensitive. The inhibition was competitive with respect to ATP and noncompetitive with respect to the phosphate acceptor poly glu4-tyr1. The degree of inhibition (IC50 = 22 microM) was however lower than that expected from a transition state analog. The compound was capable of reducing tyrosine protein kinase activity in intact cells with some selectivity at 100 microM.
authors.affiliation: Rhone-Poulenc Sånte, Centre de Recherches de Vitry, Vitry sur Seine, France.
authors.forename: I
authors.initials: I
authors.lastname: Baginski
authors.forename: A
authors.initials: A
authors.lastname: Commerçon
authors.forename: B
authors.initials: B
authors.lastname: Tocqué
authors.forename: G
authors.initials: G
authors.lastname: Colson
authors.forename: A
authors.initials: A
authors.lastname: Zerial
mesh_terms: D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001358:Avian Sarcoma Viruses; D001665:Binding Sites; D001667:Binding, Competitive; D002461:Cell Line, Transformed; D036341:Intercellular Signaling Peptides and Proteins; D015394:Molecular Structure; D009132:Muscles / Q000201:enzymology; D010455:Peptides / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011784:Quail
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010710:Phosphates; C062230:4-tolyloxycarbonyl-2-ethyl adenosine monophosphate; C027606:L-glutamic acid-L-tyrosine copolymer; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C