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A selective inhibitor Gal-PUGNAc of human lysosomal beta-hexosaminidases modulates levels of the ganglioside GM2 in neuroblastoma cells.
Stubbs, Keith A; Macauley, Matthew S; Vocadlo, David J.
Angew Chem Int Ed Engl ; 48(7): 1300-3, 2009.
Article in English | MEDLINE | ID: mdl-19130519

ABSTRACT

Gal-PUGNAc (see picture), a highly selective inhibitor for beta-hexosaminidases HEXA and HEXB is cell-permeable and modulates the activity of HEXA and HEXB in tissue culture, increasing ganglioside GM2 levels. Gal-PUGNAc should allow the role of these enzymes to be studied at the cellular level without generating a complex chemical phenotype from concomitant inhibition of O-GlcNAcase.


Subject(s)
G(M2) Ganglioside/metabolism , Neuroblastoma/enzymology , beta-N-Acetylhexosaminidases/antagonists & inhibitors , beta-N-Acetylhexosaminidases/metabolism , Cell Line, Tumor , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , G(M2) Ganglioside/chemistry , Hexosaminidase A/antagonists & inhibitors , Hexosaminidase A/metabolism , Hexosaminidase B/antagonists & inhibitors , Hexosaminidase B/metabolism , Humans , Lysosomes/enzymology , Substrate Specificity
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