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      Nucleotide Sugars in Chemistry and Biology

      review-article
      Molecules
      MDPI
      nucleotide sugar, glycosylation, glycoconjugate, mechanism, reactivity, synthesis, chemoenzymatic synthesis

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          Abstract

          Nucleotide sugars have essential roles in every living creature. They are the building blocks of the biosynthesis of carbohydrates and their conjugates. They are involved in processes that are targets for drug development, and their analogs are potential inhibitors of these processes. Drug development requires efficient methods for the synthesis of oligosaccharides and nucleotide sugar building blocks as well as of modified structures as potential inhibitors. It requires also understanding the details of biological and chemical processes as well as the reactivity and reactions under different conditions. This article addresses all these issues by giving a broad overview on nucleotide sugars in biological and chemical reactions. As the background for the topic, glycosylation reactions in mammalian and bacterial cells are briefly discussed. In the following sections, structures and biosynthetic routes for nucleotide sugars, as well as the mechanisms of action of nucleotide sugar-utilizing enzymes, are discussed. Chemical topics include the reactivity and chemical synthesis methods. Finally, the enzymatic in vitro synthesis of nucleotide sugars and the utilization of enzyme cascades in the synthesis of nucleotide sugars and oligosaccharides are briefly discussed.

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          Most cited references200

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          The bacterial cell envelope.

          The bacteria cell envelope is a complex multilayered structure that serves to protect these organisms from their unpredictable and often hostile environment. The cell envelopes of most bacteria fall into one of two major groups. Gram-negative bacteria are surrounded by a thin peptidoglycan cell wall, which itself is surrounded by an outer membrane containing lipopolysaccharide. Gram-positive bacteria lack an outer membrane but are surrounded by layers of peptidoglycan many times thicker than is found in the gram-negatives. Threading through these layers of peptidoglycan are long anionic polymers, called teichoic acids. The composition and organization of these envelope layers and recent insights into the mechanisms of cell envelope assembly are discussed.
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            Assembly of asparagine-linked oligosaccharides.

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              Lipopolysaccharide endotoxins.

              Bacterial lipopolysaccharides (LPS) typically consist of a hydrophobic domain known as lipid A (or endotoxin), a nonrepeating "core" oligosaccharide, and a distal polysaccharide (or O-antigen). Recent genomic data have facilitated study of LPS assembly in diverse Gram-negative bacteria, many of which are human or plant pathogens, and have established the importance of lateral gene transfer in generating structural diversity of O-antigens. Many enzymes of lipid A biosynthesis like LpxC have been validated as targets for development of new antibiotics. Key genes for lipid A biosynthesis have unexpectedly also been found in higher plants, indicating that eukaryotic lipid A-like molecules may exist. Most significant has been the identification of the plasma membrane protein TLR4 as the lipid A signaling receptor of animal cells. TLR4 belongs to a family of innate immunity receptors that possess a large extracellular domain of leucine-rich repeats, a single trans-membrane segment, and a smaller cytoplasmic signaling region that engages the adaptor protein MyD88. The expanding knowledge of TLR4 specificity and its downstream signaling pathways should provide new opportunities for blocking inflammation associated with infection.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                06 December 2020
                December 2020
                : 25
                : 23
                : 5755
                Affiliations
                Department of Chemistry, University of Turku, 20014 Turku, Finland; satu.mikkola@ 123456utu.fi
                Author information
                https://orcid.org/0000-0002-5149-0252
                Article
                molecules-25-05755
                10.3390/molecules25235755
                7729866
                33291296
                47913682-3b5e-4500-a9f3-30b6791d4b3c
                © 2020 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 November 2020
                : 04 December 2020
                Categories
                Review

                nucleotide sugar,glycosylation,glycoconjugate,mechanism,reactivity,synthesis,chemoenzymatic synthesis

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