Application | Comment | Organism |
---|---|---|
drug development | inhibition of DPMS is a promising strategy for the development of anti-trypanosomal agents. Thiazolidinones [(5Z)-5-[[4-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid, [(5Z)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid and [(5Z)-5-[(2-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid in particular are promising candidates for further development because of their respective activities against trypanosomal DPMS and GPI anchor biosynthesis | Trypanosoma brucei |
Cloned (Comment) | Organism |
---|---|
full-length DPMS expressed in Escherichia coli | Trypanosoma brucei |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | DPMS inhibitors prevent the biosynthesis of glycosylphosphatidylinositol anchors, and possess trypanocidal activity against live trypanosomes | Trypanosoma brucei | |
[(5Z)-4-oxo-5-(phenylmethylidene)-2-thioxo-1,3-thiazolidin-3-yl]acetic acid | 42% residual DPMS activity in the presence of 1 mM | Trypanosoma brucei | |
[(5Z)-5-[(2-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid | 23% residual DPMS activity in the presence of 1 mM. Does not affect dolichyl D-mannosyl phosphate production in the cell-free system, but potently inhibits formation of mannosylated glycosylphosphatidylinositol intermediates | Trypanosoma brucei | |
[(5Z)-5-[(3-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid | 90% residual DPMS activity in the presence of 1 mM | Trypanosoma brucei | |
[(5Z)-5-[(4-chlorophenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid | 86% residual DPMS activity in the presence of 1 mM | Trypanosoma brucei | |
[(5Z)-5-[(4-cyanophenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid | 73% residual DPMS activity in the presence of 1 mM | Trypanosoma brucei | |
[(5Z)-5-[(4-ethynylphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid | 94% residual DPMS activity in the presence of 1 mM | Trypanosoma brucei | |
[(5Z)-5-[(4-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid | 70% residual DPMS activity in the presence of 1 mM. Abolishes the formation of dolichyl D-mannosyl phosphate almost completely, and significantly reduces the formation of downstream glycosylphosphatidylinositol intermediates | Trypanosoma brucei | |
[(5Z)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid | 20% residual DPMS activity in the presence of 1 mM. Abolishes the formation of dolichyl D-mannosyl phosphate almost completely, and significantly reduces the formation of downstream glycosylphosphatidylinositol intermediates | Trypanosoma brucei | |
[(5Z)-5-[[3-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid | 23% residual DPMS activity in the presence of 1 mM | Trypanosoma brucei | |
[(5Z)-5-[[4-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid | 10% residual DPMS activity in the presence of 1 mM. Does not affect dolichyl D-mannosyl phosphate production in the cell-free system, but potently inhibits formation of mannosylated glycosylphosphatidylinositol intermediates | Trypanosoma brucei |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Trypanosoma brucei | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
GDP-mannose + dolichyl phosphate | - |
Trypanosoma brucei | GDP + dolichyl D-mannosyl phosphate | - |
? | |
additional information | glycosylphosphatidylinositol anchor biosynthesis | Trypanosoma brucei | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
dolicholphosphate mannose synthase | - |
Trypanosoma brucei |
DPMS | - |
Trypanosoma brucei |