Folylpolyglutamate analogs can inhibit casein kinase II from Xenopus laevis.
Polyglutamate analogs of folate and related compounds were tested as inhibitors of casein kinase II (CK II) obtained from Xenopus laevis. The inhibitory capacity of the pteroyl, 4-amino-10-methyl pteroyl (the methotrexate aromatic moiety), and p-aminobenzoil derivatives increased as the number of gamma-glutamates attached went from 2 to 7. The nature of the aromatic head, group was also important since hexa-gamma-glutamatic acid had no inhibitory activity while the folylhexaglutamate derivatives were strong inhibitors with relative potency of methotrexate greater than pteroyl greater than p-aminobenzoic acid. The inhibition of CK II by methotrexate gamma-pentaglutamate was competitive with casein and showed an apparent K(i) of 90 microM.
Tellez
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R
Departamento de Bioquímica, Facultad de Medicina, Universidad de Chile, Santiago.
Allende
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CC
Allende
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JE
D000818:Animals; D047390:Casein Kinase II; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000494:pharmacology; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014982:Xenopus laevis
D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D008727:Methotrexate