title: Irreversible inhibitors and activity-based probes as research tools in chemical glycobiology.
abstract: In this review, we will discuss the enzymes that are involved in the synthesis and degradation of glycoconjugates and we will give an overview of the inhibitors and activity-based probes (ABPs) that have been used to study these. Following discussion of some general aspects of the biosynthesis and degradation of N-linked glycoproteins, attention is focused on the enzymes that hydrolyze the protein-carbohydrate linkage, peptide N-glycanase and glycosylasparaginase and their mechanism. We then focus on the biosynthesis of O-linked glycoproteins and glycolipids and in particular on the enzymes that hydrolyze the interglycosidic linkages in these, the glycosidases. Some important mechanism-based glycosidase inhibitors that form a covalent bond with the targeted enzyme(s), their corresponding ABPs and their application to study this class of enzymes are highlighted. Finally, alternative pathways for degradation of glycoconjugates and an ABP-based strategy to study these will be discussed.
authors.affiliation: Whitehead Institute For Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Witte
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: Johannes M F G
authors.initials: JM
authors.lastname: Aerts
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
mesh_terms: D000818:Animals; D001227:Aspartylglucosylaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006001:Glycoconjugates / Q000378:metabolism*; D054794:Glycomics / Q000379:methods*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006001:Glycoconjugates; D006026:Glycoside Hydrolases; D001227:Aspartylglucosylaminase; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase