Inhibition of chicken liver 5-aminoimidazole-4-carboxamide ribonucleotide transformylase by 5,8-dideaza analogues of folic acid.
A series of fourteen 5,8-dideaza analogues of folic and pteroic acids was evaluated for inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (AICAR TFase) from chicken liver. Of the 5,8-dideaza folate derivatives studies, 10-oxa-5,8-dideazafolic acid was the most potent inhibitor. The addition of one L-glutamate moiety to the gamma-carboxyl group caused a 6- to 7-fold reduction in Ki in three instances. Two compounds devoid of an L-glutamate were 4- to 6-fold less inhibitory than their parent counterparts possessing one L-glutamate residue.
Mueller
W T
WT
Department of Chemistry, Pennsylvania State University, University Park 16802.
Smith
G K
GK
Benkovic
S J
SJ
Hynes
J B
JB
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002645:Chickens; D005492:Folic Acid / Q000031:analogs & derivatives*; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D019877:Hydroxymethyl and Formyl Transferases; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D051027:Phosphoribosylaminoimidazolecarboxamide Formyltransferase; D013329:Structure-Activity Relationship
D005493:Folic Acid Antagonists; D005492:Folic Acid; D019877:Hydroxymethyl and Formyl Transferases; D051027:Phosphoribosylaminoimidazolecarboxamide Formyltransferase; D000217:Acyltransferases