title: Dichloroaromatic phosphoguanidines are potent inhibitors but very poor substrates for cytosolic creatine kinase.
abstract: New phosphorylated guanidines have been synthesized and examined as potential inhibitors for creatine kinase. These compounds show a significant increase of inhibitory activity in comparison with the corresponding guanidines. Unlike the guanidines, they are competitive inhibitors because of the phosphoryl group. N-Phospho-N'-2-(2,6-dichlorophenyl)ethylguanidine is a potent inhibitor (K(i) = 2.0 mM and 1.2 mM respectively for muscle and brain-type creatine kinase). Although these phosphorylated analogs of creatine phosphate have a very poor substrate activity in the reverse reaction, the phosphoryl group is important for binding to the enzyme.
authors.affiliation: Laboratoire de Biochimie C, Hôpital Edouard Herriot, Lyon, France.
authors.forename: K L
authors.initials: KL
authors.lastname: Min
authors.forename: J P
authors.initials: JP
authors.lastname: Steghens
authors.forename: R
authors.initials: R
authors.lastname: Henry
authors.forename: A
authors.initials: A
authors.lastname: Doutheau
authors.forename: C
authors.initials: C
authors.lastname: Collombel
mesh_terms: D001921:Brain / Q000201:enzymology; D003402:Creatine Kinase / Q000037:antagonists & inhibitors*; D003600:Cytosol / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D009132:Muscles / Q000201:enzymology; D010725:Phosphocreatine / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D010725:Phosphocreatine; D003402:Creatine Kinase