Proteoglycans are glycoconjugates in which specific glycan chains are attached to core proteins, and they regulate diverse biological processes at the cell surface and in the extracellular matrix. Recent studies have clarified the molecular mechanisms involved in the initiation, elongation, sulfation, and termination of glycan biosynthesis on proteoglycans. This article provides an overview of proteoglycan biosynthesis in mammalian cells, with emphasis on recent advances. ...and more
Endo-β-N-acetylglucosaminidase (ENGase) hydrolytically cleaves the glycosidic linkage in the N,N’-diacetylchitobiose moiety of the core region of N-linked glycans (N-glycans), and it has long been widely used as a tool for structural analysis of N-glycans. It has been suggested that cytosolic ENGases, which are widely distributed in animal cells including human cells, are involved in the degradation of free N-linked glycans (FNGs), but recently the ability of cytosolic ENGases to act directly on proteins has also been shown. While Engase-knockout (KO) mice show no particular phenotypes, deletion of the Engase gene can partially suppress embryonic lethality caused by gene knock-out of the Ngly1 gene, which encodes peptide:N-glycanase (PNGase), i.e., another cytosolic deglycosylating enzyme acting on N-glycans. ENGase is thus attracting attention as a potential drug target for NGLY1 deficiency, a rare human genetic disorder. Recently, part of the molecular mechanism by which ENGase suppresses the phenotype in Ngly1-KO mice has been clarified, revealing that it is quite complex, involving the E3 ubiquitin ligase complex SCFFBS2- ARIH1. ...and more
Glycopolymers are functional polymers that strongly interact with carbohydrate-binding proteins owing to the cluster glycoside effect, which arises from the high-density arrangement of saccharide moieties along their side chains. Traditionally, most glycopolymers have been synthesized in organic solvents. However, increasing attention has recently been directed toward aqueous synthesis because of safety considerations and the need to reduce environmental impact. This review provides an overview of representative methods for glycopolymer synthesis and introduces post-polymerization modifications using water-soluble activated esters, as well as one-pot syntheses of glycopolymers from unprotected sugars via chemoenzymatic methods in water. These approaches demonstrate new possibilities for the sustainable synthesis of glycopolymers in water. ...and more
Heparan sulfate (HS) is a long linear glyco-chain component of proteoglycans on cell surfaces and within the extracellular matrix in most animal species, ranging from hydra to humans. HS regulates various physiological processes by interaction with numerous proteins including growth factors, morphogens, cytokines, receptors, enzymes, and extracellular matrix proteins. Additionally, some pathogens exploit HS on the host cell surface as a receptor for invasion. HS has a complex structure consisting of a mixture of regions with high-density, heterogeneous sulfation and regions with almost no sulfate groups. The binding specificity of HS for each functional protein is thought to be dependent on the specific arrangement of sulfate groups within the sulfated regions. ...and more
