Dichloroaromatic phosphoguanidines are potent inhibitors but very poor substrates for cytosolic creatine kinase.
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.
Min
K L
KL
Laboratoire de Biochimie C, Hôpital Edouard Herriot, Lyon, France.
Steghens
J P
JP
Henry
R
R
Doutheau
A
A
Collombel
C
C
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
D004791:Enzyme Inhibitors; D006146:Guanidines; D010725:Phosphocreatine; D003402:Creatine Kinase