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This article explores the development of glycosyltransferase inhibitors, specifically focusing on FUT8 inhibitors. FUT8 is an enzyme that plays a crucial role in various biological processes. The researchers used diversity-oriented synthesis (DOS) to create compound libraries of FUT8 inhibitors. Through late-stage functionalization and the combination of glycosyl donor and acceptor mimics, they successfully developed a FUT8 inhibitor. The study also discusses the modification of guanine derivatives and the creation of bi-substrate mimics, which are expected to exhibit exceptional selectivity among FUTs. Overall, this article presents an efficient methodology for optimizing the structure of middle molecules. [Extracted from the article]

Abstract: The chemical synthesis of a bisecting N‐acetylglucosamine (GlcNAc)‐containing N‐glycan was achieved by a convergent synthetic route through [4+2] and [6+2] glycosylations. This synthetic route reduced the number of reaction steps, although the key glycosylations were challenging in terms of yields and selectivities owing to steric hindrance at the glycosylation site and a lack of neighboring group participation. The yields of these glycosylations were enhanced by stabilizing the oxocarbenium ion intermediate through ether coordination. Glycosyl donor protecting groups were explored in an effort to realize perfect α selectivity by manipulating remote participation. The simultaneous glycosylations of a tetrasaccharide with two disaccharides was investigated to efficiently construct a bisecting GlcNAc‐containing N‐glycan. [ABSTRACT FROM AUTHOR]

The core fucose, a major modification of N-glycans, is implicated in immune regulation, such as the attenuation of the antibody-dependent cell-mediated cytotoxicity of antibody drugs and the inhibition of anti-tumor responses via the promotion of PD-1 expression on T cells. Although the core fucose regulates many biological processes, no core fucose recognition molecule has been identified in mammals. Herein, we report that Dectin-1, a known anti-β-glucan lectin, recognizes the core fucose on IgG antibodies. A combination of biophysical experiments further suggested that Dectin-1 recognizes aromatic amino acids adjacent to the N-terminal asparagine at the glycosylation site as well as the core fucose. Thus, Dectin-1 appears to be the first lectin-like molecule involved in the heterovalent and specific recognition of characteristic N-glycans on antibodies., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The chemical synthesis of a bisecting N-acetylglucosamine (GlcNAc)-containing N-glycan was achieved by a convergent synthetic route through [4+2] and [6+2] glycosylations. This synthetic route reduced the number of reaction steps, although the key glycosylations were challenging in terms of yields and selectivities owing to steric hindrance at the glycosylation site and a lack of neighboring group participation. The yields of these glycosylations were enhanced by stabilizing the oxocarbenium ion intermediate through ether coordination. Glycosyl donor protecting groups were explored in an effort to realize perfect α selectivity by manipulating remote participation. The simultaneous glycosylations of a tetrasaccharide with two disaccharides was investigated to efficiently construct a bisecting GlcNAc-containing N-glycan., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)