Chemical Regulation of Glycosylation Processes

Abstract

Glycans (monosaccharides and oligosaccharides) and their conjugates (glycoproteins, glycolipids, and proteoglycans) are structurally diverse biomolecules that are involved in many biological processes of health and disease. The structural diversity of glycans and glycoconjugates is owed to their monosaccharide composition, anomeric state, glycosidic linkage, modification (phosphorylation, sulfation, acetylation, etc.) and aglycone (protein, lipid, etc.). These diverse structures are controlled by complex glycosylation processes in cells, which are mediated by various glycosyltransferases and glycosidases. Glycosylation processes can be chemically regulated by inhibition of glycosyltransferases or glycosidases with natural and synthetic molecules. Treatment of cells with inhibitors of these enzymes results in the production of glycans or glycoconjugates containing missing or altered glycan chains. This approach is highly useful for examining the potential functional role(s) of glycans and glycoconjugates in cells or tissues, and in biological processes of health and disease. Eventually, it will provide novel mechanisms for disease treatment. This review highlights recent developments in chemical regulation of glycosylation processes with specific targets including: inhibition of (1) Nglycosylation, (2) O-glycosylation, (3) O-linked GlcNAc glycosylation, (4) proteoglycan biosynthesis, (5) glycolipid biosynthesis, and (6) terminal glycosylation. The goal of this review is to provide researchers with more competent choices in their research and lay a foundation on which continued advancements can be made to promote further explorations in glycoscience and biomedical research and applications.

Small molecule inhibitors of mammalian glycosylation

“…CMP-Neu5Ac is then transferred to the Golgi where sialyltransferases facilitate the transfer of sialic acids from the donor substrate to various glycoconjugates. Twenty sialyltransferases have been identified so far, which can be classified according to their acceptor substrates and their linkage specificities into four families ( Table 1 ) [357] . Sialic acids modify a range of glycoconjugates and are involved in pathways relating to multicellular communication [4] .…”

Carbohydrate- and Chain Length-Controlled Complexation of Carbon Nanotubes by Glycopolymers

“…Glycopolymers, namely, polymers with carbohydrate pendant groups, have been extensively used as glycoconjugate mimetics for different biological applications. − It is generally accepted that synthetic glycopolymers can mimic the functions of naturally occurring glycoconjugates , and have been employed for biosensor and drug delivery applications and biofunctionalization of nanomaterials of different interests. , Noncovalent complexation of SWCNTs by glycopolymers is of interest because of the potential of polymer backbone to form a wrapping structure on the nanotube surface, while hydrophilic groups are exposed to water for entropic stabilization of polymer–SWCNT complexes. Synthetic glycopolymers also provide greater structural tunability compared to natural glycoconjugates.…”

Glycopolymer-Wrapped Carbon Nanotubes Show Distinct Interaction of Carbohydrates With Lectins

“…We have previously reported the creation of stable and water-soluble glycopolymer-wrapped single-wall carbon nanotubes (Glyco-SWCNTs) through the noncovalent complexation of nanotubes with polymers, where the interaction of glycopolymers with SWCNTs is strongly dependent on the carbohydrate identity, ligand density, and the polymer chain length ( Cantwell et al, 2020 ). Synthetic glycopolymers with highly tunable carbohydrate structures are chemically stable and can be used as glycoconjugate mimetics for many biological applications ( Sun 2018 ; Chan et al, 2020 ). The multivalency of glycopolymers together with the tunability in polymer chain length, ligand composition and density, flexibility, and conformation promotes strong carbohydrate-mediated interactions with lectins ( Kumar et al, 2011 ; Narla et al, 2012 ; Miura et al, 2016 ; Tang et al, 2017 ).…”