Specific inhibition of acid proteinase secretion in Candida albicans by Lys-Nva-FMDP.
Secretion of aspartic (acid) proteinase by Candida albicans is inhibited by the action of a new anticandidal agent, L-lysyl-L-norvalyl-[N3-(4-methoxyfumaroyl)]-L-2,3-diamino pro panoic acid (Lys-Nva-FMDP), at low, even sub-minimum inhibitory concentrations. The observed phenomenon is a direct consequence of inhibition of the enzyme, glucosamine-6-phosphate synthase. As a result of this inhibition, biosynthesis of candidal mannoproteins is markedly reduced. A possible correlation between general inhibition of mannoprotein biosynthesis and acid proteinase secretion is suggested. The reported inhibition of acid proteinase secretion by Lys-Nva-FMDP is more specific than the previously described effects of methyl patricin, 5-fluorocytosine and fenticonazole.
Milewski
S
S
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdansk, Poland.
Mignini
F
F
Covelli
I
I
Borowski
E
E
D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D005650:Fumarates / Q000494:pharmacology*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
D005650:Fumarates; D015091:beta-Alanine; C056276:N(3)-(4-methoxyfumaroyl)-2,3-diaminopropionic acid; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D016282:Aspartic Acid Endopeptidases