Yuji Nishiura

California Institute of Technology

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Discovery of a new sialic acid binding region that regulates Siglec-7

Scientific Reports (2020)

Nao Yamakawa Yu Yasuda Atsushi Yoshimura Ami Goshima Paul R. Crocker

Abstract Siglec-7 is a human CD33-like siglec, and is localised predominantly on human natural killer (NK) cells and monocytes. Siglec-7 is considered to function as an immunoreceptor in a sialic acid-dependent manner. However, the underlying mechanisms linking sialic acid-binding and function remain unknown. Here, to gain new insights into the ligand-binding properties of Siglec-7, we carried out in silico analysis and site-directed mutagenesis, and found a new sialic acid-binding region (site 2 containing R67) in addition to the well-known primary ligand-binding region (site 1 containing R124). This was supported by equilibrium dialysis, STD-NMR experiments, and inhibition analysis of GD3-binding toward Siglec-7 using synthetic sialoglycoconjugates and a comprehensive set of ganglioside-based glycoconjugates. Our results suggest that the two ligand-binding sites are potentially controlled by each other due to the flexible conformation of the C-C′ loop of Siglec-7.

SIGLEC

Glycoconjugate

Ganglioside

CD22

Glycobiology

10.1038/s41598-020-64887-4

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Citations (35)

Developmental stage-dependent expression of an 2,8-trisialic acid unit on glycoproteins in mouse brain

Glycobiology (2010)

E. Inoko Yuji Nishiura Hiroshi Tanaka Takashi Takahashi Kiyoshi Furukawa

The monoclonal antibody mAb.A2B5 is a marker for the detection of oligodendrocyte progenitor cells that differentiate into type-2 astrocytes and oligodendrocytes. It is also a useful antibody for separating these cells from other lineage populations. The epitope of this antibody is considered to be the gangliosides GT3 and GQ1c. In this study, we sought to define more precisely the structure of the epitope. Accordingly, we chemically synthesized defined oligosialic acid structures linked to phosphatidylethanolamine and bovine serum albumin and used these to determine the antigenic specificity. mAb.A2B5 recognized the Neu5Acα2→8Neu5Acα2→8Neu5Acα→ structure on both glycolipids and glycoproteins. We then examined whether the mAb.A2B5 epitope exists on glycoproteins in developing mouse brains. Western blot analyses revealed the expression of four glycoproteins reactive with the mAb.A2B5, and their expression was dependent on the stage of neural development. All the immunoreactivity in these glycoproteins with mAb.A2B5 disappeared after sialidase treatment and were resistant to chloroform/methanol extraction. These epitopes were also detected in brain homogenates from both GD3 synthetase-null and GD3/GD2 synthetase double null mice. These findings show that the α2,8-trisialic acid (triSia) unit recognized by mAb.A2B5 resides not only on gangliosides but also on glycoproteins in developing mouse brain. We postulate that the triSia structure on glycoproteins may be involved in oligodendrocyte differentiation, similar to the case with the α2,8-triSia structure on gangliosides. Real time polymerase chain reaction analysis of the developmental expression of all known ST8Sia genes, which are responsible for the biosynthesis of α2,8-linked Sia residues, showed that ST8Sia III gene expression correlated with expression of the triSia epitope. We suggest that ST8Sia III is the principal sialyltransferase responsible for synthesis of the α2,8-triSia units on glycoproteins.

10.1093/glycob/cwq049

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Citations (48)

The existence of travelling waves for phase field equations and convergence to sharp interface models in the singular limit

Quarterly of Applied Mathematics (1991)

Gunduz Caginalp Yuji Nishiura

Interface (matter)

10.1090/qam/1096237

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Citations (35)

P-500 Stereoselective Synthesis of Oligo-α-(2,8) and (2,9) Sialic Acids

International Symposium on the Chemistry of Natural Products (2006)

Hiroshi Tanaka Yuji Nishiura Takashi Takahashi

Source

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Citations (0)

Identification of a novel and orally available benzimidazole derivative as an NPY Y5 receptor antagonist with in vivo efficacy

Bioorganic & Medicinal Chemistry Letters (2012)

Yuusuke Tamura Naoki Omori Naoki Kouyama Yuji Nishiura Kyouhei Hayashi

ADME

Benzimidazole

Linker

Lead compound

10.1016/j.bmcl.2012.09.025

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Citations (14)

Discovery of a novel olefin derivative as a highly potent and selective acetyl-CoA carboxylase 2 inhibitor with in vivo efficacy

Bioorganic & Medicinal Chemistry Letters (2018)

Yuji Nishiura Akira Matsumura Naotake Kobayashi Atsuyuki Shimazaki Shingo Sakamoto

Acetyl-CoA Carboxylase

Linker

Alkyne

Lead compound

Derivative (finance)

Structure–activity relationship

10.1016/j.bmcl.2018.05.055

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Citations (12)

Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Lactams: Enantioselective Construction of All-Carbon Quaternary Stereocenters in Saturated Nitrogen-Containing Heterocycles

Organic Letters (2023)

Tianyi Zhang Yuji Nishiura Alexander Q. Cusumano Brian M. Stoltz

Stereogenic nitrogen-containing heterocycles are ubiquitous in natural products and pharmaceutical compounds, but methods for their enantioselective construction have remained elusive. We report a general method for the asymmetric conjugate addition of arylboronic acids to β-alkyl/aryl α,β-unsaturated lactams that affords chiral β,β-disubstituted lactams. The transformation is operationally simple and air- and moisture-tolerant and uses a commercially available (S)-t-Bu-PyOx ligand. The method is high-yielding (up to 95% yield) and enantioselective (up to 97% ee) for a wide range of arylboronic acids and α,β-unsaturated lactams, including those with different ring sizes.

Stereocenter

Conjugate

10.1021/acs.orglett.3c02064

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Citations (3)

An Efficient Convergent Synthesis of GP1c Ganglioside Epitope

Journal of the American Chemical Society (2008)

Hiroshi Tanaka Yuji Nishiura Takashi Takahashi

In this report, we describe an efficient convergent synthesis of the GP1c glycolipid epitope, which is one of the most complex c-series gangliosides. The α(2,3) and α(2,8) sialylations were accomplished by use of 5N,4O-carbonyl and 7,8-O-isopropyliden as well as 5N,4O-carbonyl- and 7,8-di-O-chloroacetyl-protected sialyl donors in good yields with excellent α-selectivity, respectively. The two sialyl donors enable synthesis of the di- and trisialylgalactosides by simple glycosylation and deprotection. We synthesized the protected GP1c glycolipid epitope, which is a compact, rigid, branched structure, via direct coupling of tetarasaccharide and pentasaccharide units.

Ganglioside

Convergent synthesis

10.1021/ja807482t

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Citations (66)

4-Octyloxybiphenyl-4'-yl 4-Methoxybenzoate

Acta Crystallographica Section C Crystal Structure Communications (1996)

K. Hori Yuji Nishiura

The title compound, C28H32O4, has the phase sequence of crystal–nematic -isotropic liquid. The crystal has an `imbricated' structure, i.e. a half-and-half overlapping of molecules. Molecular long axes are oriented in one direction, resulting in a polar structure.

Sequence (biology)

Crystal (programming language)

Chemical polarity

10.1107/s0108270196008517

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Citations (1)

Synthetic Study of a(2,8) Oligosialoside Using N-Troc Sialyl N-Phenyltrifluoroimidate

Heterocycles (2006)

Takashi Takahashi Hiroshi Tanaka Yuji Nishiura Masaatsu Adachi

An effective approach for the synthesis of oligo-α(2,8) sialosides using N-Troc sialyl donors is described.Glycosylation of N-Troc sialoside with N-Troc sialyl N-phenyltrifluoroimidate and phosphites smoothly proceeded to provide α(2,8) disialosides in good yield and selectivity.Sialic acids such as Neu5Ac, Neu5Gc and KDN, are often located at the non-reducing end of glycoconjugates on the cell surface through α-glycosidic bonds, and play a central role in cell surface recognition phenomena. 1Recently, poly-and oligo-sialosides composed of the α(2,8) disialyl unit (1) are found in many glycoproteins as well as glycolipids, and would be important fragments to bind proteins as well as monomeric sialic acid. 2 However, low availability of the pure sialo-containing glycoconjugates from the natural sources makes it difficult to elucidate their biological activity, and requires an effective methodology for the synthesis of α(2,8) sialosides.

Glycoconjugate

Glycosidic bond

10.3987/com-05-s(t)30

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Citations (43)