The University of Osaka · Biochemistry, Genetics and Molecular Biology
Professor Shinya Hanashima's research lab specializes in the chemical synthesis and structural elucidation of biologically active glycans, with a focus on sialylated and sulfated glycolipids. The lab develops innovative synthetic methodologies—particularly stereoselective sialylation and glycosylation techniques—enabling the efficient construction of complex oligosaccharides, including tumor-associated antigens and glycoconjugates with therapeutic potential. Key research directions include the design of glycosyltransferase inhibitors and the structure-activity relationship studies of natural and synthetic glycolipids, such as sulfoquinovosylglycerol derivatives, for anti-cancer and enzyme-inhibitory applications. The lab integrates solid-phase synthesis, polymer-supported strategies, and advanced protecting group chemistry to achieve high-yielding, selective glycan assembly.
Figures are computed from collected data and may differ slightly.
[reaction: see text] The ubiquity of the sialic acid alpha(2-3) galactose linkage in oligosaccharides of biological relevance necessitates a building block for the incorporation of this motif into oligosaccharides prepared by modular synthesis. The linear synthesis of the sialyl Lewis X tumor-associated antigen (1) has been accomplished in good yield using a sialic acid alpha(2-3) galactose disaccharide building block. The disaccharide building block was synthesized efficiently from readily avai
We reported previously that sulfolipids in the sulfoquinovosylacylglycerol class from a fern and an alga are potent inhibitors of DNA polymerase alpha and beta and potent anti-neoplastic agents. In developing a procedure for chemical synthesis of sulfolipids, we synthesized many derivatives and stereoisomers of sulfoquinovosylmonoacylglycerol (SQMG) / sulfoquinovosyldiacylglycerol (SQDG). Some of these molecules were stronger inhibitors than the SQMG / SQDG originally reported as natural compoun
Carbo loading! The synthesis of α(2,3)- or α(2,6)-sialylated biantennary glycans is possible with a new approach. The common precursor 1 was synthesized with a soluble polymer support strategy (a) in combination with a resin capture–release protocol. Hexasaccharide 1 can then be diverged to various polysaccharides by enzymatic glycosylation (b). Bn=benzyl, TBS=tert-butyldimethylsilyl.
Abstract We describe efficient sialylation reactions in CH 2 Cl 2 with the use of silylene/oxazolidinone double‐locked sialic acid building blocks. The building blocks were synthesized from 4,5‐oxazolidinone‐protected phenylthiosialoside. In sialylation reactions towards primary and relatively reactive secondary hydroxy groups on the galactosides, the double‐locked building blocks provided desired coupling products in good yields with excellent α‐selectivities. In the sialylation reaction with t
シアル酸は哺乳動物の細胞表面に存在するシアリル化糖鎖の非還元末端に広く存在している。それらのシアル酸は細胞間の相互作用や病原性の細菌、ウイルスの感染に重要な役割を果たしている。シアリル化糖鎖の化学合成は20 年以上もの間研究されてきており、立体選択的なシアル酸のグリコシル化反応において興味深い手法が開発されている。化学酵素法に関しても立体選択的なシアル酸の導入に用いることが可能である。このミニレビューでは、ごく最近報告された化学的手法を用いた立体選択的シアリル化反応と、それらの新しい反応を用いた天然型のシアリル化糖鎖、特にオリゴシアル酸やポリシアル酸の合成に焦点をあてて紹介した。
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 chlo
Human and avian influenza type A viruses bind sialylated pentasaccharides. Herein, the total synthesis of four of these glycans is reported. Efficient sialylations relied on two N-Troc-protected (Troc = 2,2,2-trichloroethoxycarbonyl) sialic acid building blocks. The first, a thiophenyl glycoside, readily produced the sialyl-alpha(2-6)galactose disaccharide. Combination of the second building block, a novel glycosyl phosphite, and a benzylidene-protected galactoside produced the best results for
NMR-based analysis of glycans by directly observing hydroxyl protons has been difficult because of their inherently fast exchange with water. We observed hydroxyl proton exchanges in a LewisX-LewisX interaction by using deuterium isotope shifts on (13)C-NMR. This strategy is suitable for analyzing weak interactions by identifying involved protons.
ZG16p is a soluble mammalian lectin that interacts with mannose and heparan sulfate. Here we describe detailed analysis of the interaction of human ZG16p with mycobacterial phosphatidylinositol mannosides (PIMs) by glycan microarray and NMR. Pathogen-related glycan microarray analysis identified phosphatidylinositol mono- and di-mannosides (PIM1 and PIM2) as novel ligand candidates of ZG16p. Saturation transfer difference (STD) NMR and transferred NOE experiments with chemically synthesized PIM
Exosomes are small extracellular vesicles (sEVs) involved in distal cell-cell communication and cancer migration by transferring functional cargo molecules. Membrane domains similar to lipid rafts are assumed to occur in exosome membranes and are involved in interactions with target cells. However, the bilayer membrane properties of these small vesicles have not been fully investigated. Therefore, we examined the fluidity, lateral domain separation, and transbilayer asymmetry of exosome membrane
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