Microbiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Microbiology 147 (2001), 1955-1959
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zgódka, D.
Right arrow Articles by Borowski, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zgódka, D.
Right arrow Articles by Borowski, E.
Agricola
Right arrow Articles by Zgódka, D.
Right arrow Articles by Borowski, E.
Microbiology (2001), 147, 1955-1959.
© 2001 Society for General Microbiology

Biochemistry

A diffusible analogue of N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid with antifungal activity

Dorota Zgódka1, Slawomir Milewski1 and Edward Borowski1

Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdask, 11/12 Narutowicza St, 80-952 Gdask, Poland1

Author for correspondence: Edward Borowski. Tel: +48 58 347 25 23. Fax: +48 58 347 26 94. e-mail: borowski{at}altis.chem.pg.gda.pl

N3-(4-Methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP), a specific and potent inactivator of glucosamine-6-phosphate (GlcN-6-P) synthase from Candida albicans, exhibits relatively poor anticandidal activity, with an MIC value amounting to 50 µg ml-1 (200 µM). Uptake of FMDP into C. albicans cells follows saturation kinetics and is sensitive to the action of metabolic inhibitors, thus indicating the active transport mechanism. However, the acetoxymethyl ester of FMDP penetrates the fungal cell membrane by free diffusion and is rapidly hydrolysed by C. albicans cytoplasmic enzymes to release the free FMDP. This mechanism gives rise to continuous accumulation of the enzyme inhibitor and results in higher antifungal activity of the FMDP ester (MIC=3·1 µg ml-1, 10 µM). These results show that the ‘pro-drug’ approach can be successfully applied for the enhancement of antifungal activity of glutamine analogues that inhibit GlcN-6-P synthase.

Keywords: glucosamine-6-phosphate synthase, glutamine analogues, pro-drugs, diffusion, antifungal compounds

Abbreviations: FMDP, N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid; GlcN-6-P synthase, glucosamine-6-phosphate synthase; TNBS, 2,4,6-trinitrobenzenesulfonate






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
INT J SYST EVOL MICROBIOL MICROBIOLOGY J GEN VIROL
J MED MICROBIOL ALL SGM JOURNALS
Copyright © 2001 Society for General Microbiology.