Biomaterial Database

Inhibitors of UDP-galactopyranose mutase thwart mycobacterial growth. 2008

Emily C Dykhuizen, and John F May, and Aimon Tongpenyai, and Laura L Kiessling

Departments of Chemistry and Biochemistry, University of WisconsinMadison, Madison, Wisconsin 53706, USA.

Galactofuranose (Galf) residues are fundamental components of the cell wall of mycobacteria. A key enzyme, UDP-galactopyranose mutase (UGM), that participates in Galf incorporation mediates isomerization of UDP-Galf from UDP-galactopyranose (UDP-Galp). UGM is of special interest as a therapeutic target because the gene encoding it is essential for mycobacterial viability and there is no comparable enzyme in humans. We used structure-activity relationships and molecular design to devise UGM inhibitors. From a focused library of synthetic aminothiazoles, several compounds that block the UGM from Klebsiella pneumoniae or Mycobacterium tuberculosis were identified. These inhibitors block the growth of M. smegmatis.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008968	Molecular Conformation	The characteristic three-dimensional shape of a molecule.	Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013844	Thiazoles	Heterocyclic compounds where the ring system is composed of three CARBON atoms, a SULFUR and NITROGEN atoms.	Thiazole
D053778	Thiazolidines	Reduced (protonated) form of THIAZOLES. They can be oxidized to THIAZOLIDINEDIONES.	Thiazolidine
D019751	Intramolecular Transferases	Enzymes of the isomerase class that catalyze the transfer of acyl-, phospho-, amino- or other groups from one position within a molecule to another. EC 5.4.	Mutases,Transferases, Intramolecular