Trends in Glycoscience and Glycotechnology
Online ISSN : 1883-2113
Print ISSN : 0915-7352
ISSN-L : 0915-7352
Volume 32 , Issue 185
Showing 1-12 articles out of 12 articles from the selected issue
MINIREVIEW
  • Christopher J. Vavricka, Tatsuma Matsumoto, Hiromasa Kiyota
    2020 Volume 32 Issue 185 Pages E1-E5
    Published: January 25, 2020
    Released: January 25, 2020
    JOURNALS RESTRICTED ACCESS

    Neuraminidase (NA) inhibitors are effective at treating and preventing infections caused by epidemic and pandemic influenza viruses. The first generation of influenza NA inhibitors were inspired by the structure of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, a putative oxocarbenium ion transition state analogue. As a next-generation approach to influenza NA inhibitor design, irreversible inhibitors targeting influenza NA Tyr406 are now being explored. After proving the concept that influenza NA can be irreversibly inhibited by difluorosialic acids, substitution of the anomeric carboxy group was examined as a second novel strategy. Anomeric sulfo analogues of sialic acid (N-acetylneuraminic acid, NANA) were thereby synthesized and found to inhibit influenza NA with higher potency relative to that of the corresponding anomeric carboxy and phosphono compounds, via enhanced electrostatic interactions with the NA active site triarginyl cluster. The combination of these two novel approaches is now being pursued to produce improved irreversible NA inhibitors.

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  • Noriko Suzuki
    2020 Volume 32 Issue 185 Pages E7-E12
    Published: January 25, 2020
    Released: January 25, 2020
    JOURNALS RESTRICTED ACCESS

    To explain the diverse structures, distributions, and properties of glycans, it is necessary to study them from various perspectives. Glycans with unusual structures in humans may be found in other species, and evolutionary analyses can provide insight into the significance of glycan diversity. For instance, (Galα1-4Gal)-bearing glycoprotein expression was initially reported in pigeons and a few additional animals. However, we demonstrated that the glycoproteins with Galα1-4Gal epitopes are expressed in many birds belonging to the main avian clade (Neoaves), accounting for 95% of modern birds. We cloned cDNAs of an α1,4-galactosyltransferase, which produce this carbohydrate antigens, from a pigeon liver cDNA library, and inferred how this glycans were acquired or lost during vertebrate evolution ranging from fish to birds and mammals, based on cDNA sequences and DNA databases. Since the Human Genome Project, the availability of whole genome sequence data has grown enormously, and the number and scope of target species has expanded. Combined with dramatically improved analytical techniques for glycans, it is possible to investigate the mechanism underlying glycan diversity and the roles of various glycans acquired during vertebrate evolution.

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  • Shigeko Kijimoto-Ochiai
    2020 Volume 32 Issue 185 Pages E13-E19
    Published: January 25, 2020
    Released: January 25, 2020
    JOURNALS OPEN ACCESS

    Subtraction of sialic acids from glycans on the cell surface is important for communication between immune cells. Therefore, I hypothesized that there must be a sialidase that acts on immune cells in physiological conditions, that is, at neutral pH. Such a sialidase was examined using mouse immune tissues: the thymus, spleen and lymph node. We observed higher sialidase activity at neutral pH than acidic pH in the crude membrane fraction from the thymus but not in spleen or lymph node tissues. There is no such property among the four kinds of sialidases that have been cloned from vertebrates. We tried to clarify the true nature of the enzyme, and found NEU2-like sialidase-positive cells in the thymus histochemically using 5-bromo-4-chloro-3-indolyl-α-D-N-acetylneuraminic acid and named them Neu-medullocytes. Recently, we showed that Neu-medullocytes are CD5 positive B cells (B-1 cells), and some of them express the transcription factor autoimmune regulator (AIRE). Thus, the physiological function of these cells is probably to act as antigen-presenting cells that present carbohydrate antigens, as is characteristic of B-1 cells, during negative selection step in the thymus. The absence of autoantibodies against self-carbohydrate antigens such as blood type can be explained by the existence of these cells.

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  • Ryuichiro Suzuki, Eiji Suzuki
    2020 Volume 32 Issue 185 Pages E21-E30
    Published: January 25, 2020
    Released: January 25, 2020
    JOURNALS OPEN ACCESS

    Brancihing enzymes (BEs) catalyze the transglycosylation reactions to form a new branching point consisting of an α-1,6-glucosidic linkage by cleaving an α-1,4-glucosidic linkage of an α-glucan chain. BEs are ubiquitous throughout the prokaryotes but are only found in limited taxa in the eukaryotes. Prokaryotic and eukaryotic BEs are classified into distinct families based on similarities in their primary structures. Land plants have multiple BE isoforms, whose function in vivo has been identified using mutants. Recent studies have revealed that plant BEs form protein–protein complexes with related enzymes involved in α-glucan metabolism in vivo. Although their biological significance is unclear, it is proposed that they are essential for efficient amylopectin biosynthesis. Crystal structures of BEs from eukaryotes (rice and human) are now available. These two structures have the same domain organization, containing a catalytic domain common to all members of glycoside hydrolase family 13. Recently, the authors have reported the structures of BE from a cyanobacterium (a photosynthetic prokaryote) in complex with maltooligosaccharides at the active site. On the other hand, little is known about the structure–function relationship of eukaryotic BEs. This review describes recent progress in research on the structure and function of eukaryotic BEs.

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GLYCODEBUT
  • Taiki Kuribara
    2020 Volume 32 Issue 185 Pages E31-E34
    Published: January 25, 2020
    Released: January 25, 2020
    JOURNALS RESTRICTED ACCESS

    Glycoproteins are synthesized in the endoplasmic reticulum (ER). Glycan structures on the glycoprotein function as folding, secretion, and degradation signals. Especially in the sorting step of glycoproteins, mannose trimmings of Man9GlcNAc2 (M9) mediated by α1,2-mannosidases in the ER are involved in secretion and degradation. Several glycan isomers produced through the sorting process are assumed to be secretion and degradation signals. However, it is unclear whether these mannose trimmings occurred regioselectively or randomly. To answer this question, we found selective inhibitors of the production of secretion and degradation signals, respectively. With these selective inhibitors, mannose trimming pathway analysis was carried out. The pathway analysis results indicate that two independent mannose trimming pathways exist in the ER.

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GLYCOTOPIC
MINIREVIEW (Jpn. Ed.)
  • Christopher J. Vavricka, Tatsuma Matsumoto, Hiromasa Kiyota
    2020 Volume 32 Issue 185 Pages J1-J5
    Published: January 25, 2020
    Released: January 25, 2020
    JOURNALS RESTRICTED ACCESS

    Neuraminidase (NA) inhibitors are effective at treating and preventing infections caused by epidemic and pandemic influenza viruses. The first generation of influenza NA inhibitors were inspired by the structure of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, a putative oxocarbenium ion transition state analogue. As a next-generation approach to influenza NA inhibitor design, irreversible inhibitors targeting influenza NA Tyr406 are now being explored. After proving the concept that influenza NA can be irreversibly inhibited by difluorosialic acids, substitution of the anomeric carboxy group was examined as a second novel strategy. Anomeric sulfo analogues of sialic acid (N-acetylneuraminic acid, NANA) were thereby synthesized and found to inhibit influenza NA with higher potency relative to that of the corresponding anomeric carboxy and phosphono compounds, via enhanced electrostatic interactions with the NA active site triarginyl cluster. The combination of these two novel approaches is now being pursued to produce improved irreversible NA inhibitors.

    Download PDF (3111K)
  • Noriko Suzuki
    2020 Volume 32 Issue 185 Pages J7-J12
    Published: January 25, 2020
    Released: January 25, 2020
    JOURNALS RESTRICTED ACCESS

    To explain the diverse structures, distributions, and properties of glycans, it is necessary to study them from various perspectives. Glycans with unusual structures in humans may be found in other species, and evolutionary analyses can provide insight into the significance of glycan diversity. For instance, (Galα1-4Gal)-bearing glycoprotein expression was initially reported in pigeons and a few additional animals. However, we demonstrated that the glycoproteins with Galα1-4Gal epitopes are expressed in many birds belonging to the main avian clade (Neoaves), accounting for 95% of modern birds. We cloned cDNAs of an α1,4-galactosyltransferase, which produce this carbohydrate antigens, from a pigeon liver cDNA library, and inferred how this glycans were acquired or lost during vertebrate evolution ranging from fish to birds and mammals, based on cDNA sequences and DNA databases. Since the Human Genome Project, the availability of whole genome sequence data has grown enormously, and the number and scope of target species has expanded. Combined with dramatically improved analytical techniques for glycans, it is possible to investigate the mechanism underlying glycan diversity and the roles of various glycans acquired during vertebrate evolution.

    Download PDF (766K)
  • Shigeko Kijimoto-Ochiai
    2020 Volume 32 Issue 185 Pages J13-J18
    Published: January 25, 2020
    Released: January 25, 2020
    JOURNALS OPEN ACCESS

    Subtraction of sialic acids from glycans on the cell surface is important for communication between immune cells. Therefore, I hypothesized that there must be a sialidase that acts on immune cells in physiological conditions, that is, at neutral pH. Such a sialidase was examined using mouse immune tissues: the thymus, spleen and lymph node. We observed higher sialidase activity at neutral pH than acidic pH in the crude membrane fraction from the thymus but not in spleen or lymph node tissues. There is no such property among the four kinds of sialidases that have been cloned from vertebrates. We tried to clarify the true nature of the enzyme, and found NEU2-like sialidase-positive cells in the thymus histochemically using 5-bromo-4-chloro-3-indolyl-α-D-N-acetylneuraminic acid and named them Neu-medullocytes. Recently, we showed that Neu-medullocytes are CD5 positive B cells (B-1 cells), and some of them express the transcription factor autoimmune regulator (AIRE). Thus, the physiological function of these cells is probably to act as antigen-presenting cells that present carbohydrate antigens, as is characteristic of B-1 cells, during negative selection step in the thymus. The absence of autoantibodies against self-carbohydrate antigens such as blood type can be explained by the existence of these cells.

    Download PDF (1556K)
  • Ryuichiro Suzuki, Eiji Suzuki
    2020 Volume 32 Issue 185 Pages J19-J28
    Published: January 25, 2020
    Released: January 25, 2020
    JOURNALS OPEN ACCESS

    Brancihing enzymes (BEs) catalyze the transglycosylation reactions to form a new branching point consisting of an α-1,6-glucosidic linkage by cleaving an α-1,4-glucosidic linkage of an α-glucan chain. BEs are ubiquitous throughout the prokaryotes but are only found in limited taxa in the eukaryotes. Prokaryotic and eukaryotic BEs are classified into distinct families based on similarities in their primary structures. Land plants have multiple BE isoforms, whose function in vivo has been identified using mutants. Recent studies have revealed that plant BEs form protein–protein complexes with related enzymes involved in α-glucan metabolism in vivo. Although their biological significance is unclear, it is proposed that they are essential for efficient amylopectin biosynthesis. Crystal structures of BEs from eukaryotes (rice and human) are now available. These two structures have the same domain organization, containing a catalytic domain common to all members of glycoside hydrolase family 13. Recently, the authors have reported the structures of BE from a cyanobacterium (a photosynthetic prokaryote) in complex with maltooligosaccharides at the active site. On the other hand, little is known about the structure–function relationship of eukaryotic BEs. This review describes recent progress in research on the structure and function of eukaryotic BEs.

    Download PDF (5473K)
GLYCODEBUT (Jpn. Ed.)
  • Taiki Kuribara
    2020 Volume 32 Issue 185 Pages J29-J32
    Published: January 25, 2020
    Released: January 25, 2020
    JOURNALS RESTRICTED ACCESS

    Glycoproteins are synthesized in the endoplasmic reticulum (ER). Glycan structures on the glycoprotein function as folding, secretion, and degradation signals. Especially in the sorting step of glycoproteins, mannose trimmings of Man9GlcNAc2 (M9) mediated by α1,2-mannosidases in the ER are involved in secretion and degradation. Several glycan isomers produced through the sorting process are assumed to be secretion and degradation signals. However, it is unclear whether these mannose trimmings occurred regioselectively or randomly. To answer this question, we found selective inhibitors of the production of secretion and degradation signals, respectively. With these selective inhibitors, mannose trimming pathway analysis was carried out. The pathway analysis results indicate that two independent mannose trimming pathways exist in the ER.

    Download PDF (1356K)
GLYCOTOPIC (Jpn. Ed.)
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