N gamma-alkyl derivatives of L-glutamine as inhibitors of glutamine-utilizing enzymes.
A general, facile method to synthesize the N gamma-alkyl and N gamma,N gamma-dialkyl derivatives of L-glutamine 1a-d from L-glutamic acid as a starting substrate is presented. The obtained compounds are shown to inhibit three different glutamine-utilizing enzymes, namely: glutaminase, gamma-glutamyl transpeptidase, and glucosamine-6-phosphate synthase, with inhibitory constants within the millimolar range.
Prokop
Marta
M
Department of Organic Chemistry, Gdansk University of Technology, Narutowicza st. 11/12, 80-952, Gdansk, Poland.
Czarnecka
Justyna
J
Milewska
Maria J
MJ
D002176:Candida albicans / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005972:Glutaminase / Q000037:antagonists & inhibitors*; D005973:Glutamine / Q000737:chemistry / Q000494:pharmacology*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D005973:Glutamine; D005723:gamma-Glutamyltransferase; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D005972:Glutaminase