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Chemical probes of UDP-galactopyranose mutase.
- Source :
-
Chemistry & biology [Chem Biol] 2006 Aug; Vol. 13 (8), pp. 825-37. - Publication Year :
- 2006
-
Abstract
- Many pathogenic prokaryotes and eukaryotes possess the machinery required to assemble galactofuranose (Galf)-containing glycoconjugates; these glycoconjugates can be critical for virulence or viability. Accordingly, compounds that block Galf incorporation may serve as therapeutic leads or as probes of the function of Galf-containing glycoconjugates. The enzyme UDP-galactopyranose mutase (UGM) is the only known generator of UDP-galactofuranose, the precursor to Galf residues. We previously employed a high-throughput fluorescence polarization assay to investigate the Klebsiella pneumoniae UGM. We demonstrate the generality of this assay by extending it to UGM from Mycobacterium tuberculosis. To identify factors influencing binding, we synthesized a directed library containing a 5-arylidene-2-thioxo-4-thiazolidinone core, a structure possessing features common to ligands for both homologs. Our studies offer a blueprint for identifying inhibitors of the growing family of UGM homologs and provide insight into UGM inhibition.
- Subjects :
- Binding Sites
Galactose analogs & derivatives
Galactose chemistry
Galactose metabolism
Intramolecular Transferases antagonists & inhibitors
Klebsiella pneumoniae enzymology
Ligands
Models, Molecular
Molecular Probe Techniques
Molecular Probes chemical synthesis
Molecular Probes pharmacology
Molecular Structure
Mycobacterium tuberculosis enzymology
Structure-Activity Relationship
Thiazoles chemical synthesis
Thiazoles pharmacology
Uridine Diphosphate analogs & derivatives
Uridine Diphosphate chemistry
Uridine Diphosphate metabolism
Intramolecular Transferases chemistry
Molecular Probes chemistry
Thiazoles chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1074-5521
- Volume :
- 13
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Chemistry & biology
- Publication Type :
- Academic Journal
- Accession number :
- 16931332
- Full Text :
- https://doi.org/10.1016/j.chembiol.2006.06.007