A search for pyrophosphate mimics for the development of substrates and inhibitors of glycosyltransferases.
The design and synthesis of several beta-1,4-galactosyltransferase inhibitors are reported. Mimics of the pyrophosphate-Mn2+ complex were the focus of the design. Malonic, tartaric, and monosaccharide moieties were used as replacements of the pyrophosphate moiety, and galactose or azasugars with potent galactosidase inhibitory activity were used as the 'donor' component. Compound 6, in which glucose was used as the pyrophosphate-Mn2+ complex mimic and galactose as the 'donor' component, showed the best inhibitory activity towards the transferase with a Ki of 119.6 microM.
Wang
R
R
Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
Steensma
D H
DH
Takaoka
Y
Y
Yun
J W
JW
Kajimoto
T
T
Wong
C H
CH
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D011756:Diphosphates / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D005647:Fucosyltransferases / Q000378:metabolism*; D008314:Malonates / Q000737:chemistry; D008345:Manganese / Q000378:metabolism; D009005:Monosaccharides / Q000737:chemistry; D009237:N-Acetyllactosamine Synthase / Q000037:antagonists & inhibitors*; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D013644:Tartrates / Q000737:chemistry; D014415:Tunicamycin / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000998:Antiviral Agents; D011756:Diphosphates; D004791:Enzyme Inhibitors; D008314:Malonates; D009005:Monosaccharides; D011741:Pyrimidine Nucleosides; D013644:Tartrates; D014415:Tunicamycin; D008345:Manganese; C020789:papulacandin B; C030290:malonic acid; C011952:nikkomycin; C002458:polyoxorim; D005647:Fucosyltransferases; D009237:N-Acetyllactosamine Synthase; C029768:tartaric acid