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Shino Manabe

Publications and source records attributed to Shino Manabe.

12 recordsLinked to original sources
PubMed2006

N-benzyl-2,3-oxazolidinone as a glycosyl donor for selective alpha-glycosylation and one-pot oligosaccharide synthesis involving 1,2-cis-glycosylation.

Glycosylation reactions using N-benzyl-2,3-trans-oxazolidinones as the glycosyl donors were shown to be highly alpha-selective. Advantages of the donor include facile preparation in gram-scale preparation and simple deprotection procedures. Subsequently, a one-pot oligosaccharide synthesis involving 1,2-cis glycosidic linkages was demonstrated using the novel glycosyl donors.

Journal Article↗
PubMed2006

Systematic synthesis of bisubstrate-type inhibitors of N-acetylglucosaminyltransferases.

Bisubstrate-type inhibitors for N-acetylglucosaminyltransferase (GnT)-V and -IX were designed and synthesized. These compounds carry both an acceptor trisaccaride and an UDP-GlcNAc component tethered by a linker of variable length. The acceptor trisaccharide unit was constructed using a combination of a polymer support and a resin capture-release strategy. Namely, starting with a beta-mannoside bound to low molecular weight monomethyl PEG (MPEG), successive glycosylations with donors having chloroacetyl group produced the trisaccharide, which was subjected to the capture-release purification using cysteine loaded resin. UDP-GlcNAc units carrying phosphate moieties were separately synthesized from the bromoacetamide-containing glucosamine derivative. Ligation between the acceptor thiol and each alkyl bromide on the donor unit readily proceeded, and produced the coupling product. The introduction of the UMP component gave target compounds. All of the synthesized compounds had significant activities to GnT-V and -IX. Their potencies were dependent upon the linkers length. GnT-IX was more sensitive to these inhibitors and optimum linker length was clearly different between these GnTs. The most potent inhibitor of GnT-V had Ki=18.3 microM, while that of GnT-IX had Ki = 4.7 microM.

Carbohydrate Sequence↗
PubMed2004

Increased expression of protein C-mannosylation in the aortic vessels of diabetic Zucker rats.

C-Mannosylation is a novel type of glycosylation in proteins. There are several examples of proteins in which the specific motif Trp-X-X-Trp is mannosylated at the first Trp to produce C-mannosylated Trp (CMW). Although C-mannosylation modifies Trp-X-X-Trp, predicted to be a functional motif of various integral proteins such as cytokine receptors, the physiological or pathological relevance of C-mannosylation in the cell is still not known. In this study, to characterize C-mannosylation in biological samples, we generated specific polyclonal antibodies against CMW by using a chemically synthesized CMW as an antigen. Using the antibody, we investigated the effect of hyperglycemic conditions on protein C-mannosylation in cultured cells and diabetic Zucker fatty rats. We found that protein C-mannosylation was increased in macrophage-like RAW264.7 cells under hyperglycemic conditions compared to low-glucose conditions. Furthermore, C-mannosylation was increased in the aortic vessel wall of Zucker fatty rats. Thrombospondin-1 was identified as a protein modified with C-mannosylation, and its expression was also increased in the aortic tissues of Zucker fatty rats. These results indicate that C-mannosylation is increased in specific tissues or cell types under hyperglycemic conditions, suggesting a pathological role for the increased C-mannosylation in the development of diabetic complications.

Amino Acid Motifs↗
PubMed2003

Total synthesis of mannosyl tryptophan and its derivatives.

Glycosylation is one of the most important post- or co-translational modifications of proteins, which affects the biological activities of the parent proteins by influencing the higher-order structure. Recently, a highly novel variant of glycoproteins that incorporate a C-glycosylated amino acid was identified in various proteins. The total synthesis of one such C-glycosyl amino acid, namely, C (2)-alpha-D-C-mannosylpyranosyl-L-tryptophan and related peptides were successfully achieved. The mannose and tryptophan moieties were connected via ring opening of benzyl-protected 1,2-anhydro-mannose by a lithiated indole derivative. After the functional group conversion and deprotection steps, the glyco-amino acid was synthesized in a concise and stereoselective manner, in high overall yields. The stereoisomer, C (2)-alpha-D-C-glycosylpyranosyl-L-tryptophan was synthesized in a similar way. Furthermore, it was revealed that the intermediate azido acid can serve as a useful building block for peptide elongation. A synthetic route for the peptide bond formation of a glycopeptide, without protection of the hydroxyl groups, using the triazine salt derivative as a coupling reagent is also reported.

Mannose↗
PubMed2002

Tag-reporter and resin capture--release strategy in oligosaccharide synthesis.

Low molecular weight poly(ethylene glycol) (LWPEG) has been found to be useful as a "tag" in oligosaccharide synthesis due to its high polarity. Real-time reaction monitoring was achieved by use of MALDI-TOF MS in the glycosylation reactions and color tests in the deprotection of the chloroacetyl group. Further, a cysteine-supported insoluble resin enables the purification of the chloroacetyl-bound compounds on soluble PEG.

Combinatorial Chemistry Techniques↗
PubMed2002

[Development of novel methodology for rapid conjugated oligosaccharide synthesis].

Glycosylation is one of the most important post-translation modifications of proteins, which affects biological activities by way of controlling higher order structure. Recently, the novel structure of glycoprotein, namely C-glycosyl protein was identified in various proteins. The first total synthesis of the naturally occurring C-glycosyl amino acid and peptide was achieved. The mannose and tryptophan moiety was connected via ring opening reaction of epoxide by lithiated indole derivative. After functional group conversion and deprotection, the glyco-amino acid was synthesized in a concise and stereoselective manner. To develop the rapid oligosaccharide construction methodology, the soluble polymer supported oligosaccharide was investigated. Due to high polarity of polymer support, the purification of PEG bound compound is achieved quite easily. The real-time monitoring of the glycosylation reaction was performed by MALDI-TOF MS, whereas the deprotection reaction of chloroacetyl group was performed by color test using (p-nitrobenzyl) pyridine. The purification of PEG bound compound which has chloroacetyl group, is achieved by capture-release strategy by use of resin bound cysteine derivative. By combination of these methodologies and novel linker, tetrasaccharides were synthesized.

Methods↗
PubMed2001

Solid-Phase Capture-Release Strategy Applied to Oligosaccharide Synthesis on a Soluble Polymer Support This work was supported in part by the Mizutani Foundation for Glycoscience (grant to Y.I.), the RIKEN Presidential Fund (grant to S.M.), and the Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Scientific Research to S.M.). We thank Dr. Teiji Chihara and his staff for the elemental analyses, Ms. Yasuko Tanaka for her contribution at the exploratory stage of this work, and Ms. Akemi Takahashi for her technical assistance.

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Journal Article↗