Yoshiyuki Manabe

The photobromination of C-H bonds by using molecular bromine was reinvestigated under microfluidic conditions. The continuous-flow method suppressed the production of dibrominated compounds and effectively produced the desired monobrominated products with high selectivity. Rapid bromination of benzylic substrates containing a photoaffinity azide group was achieved without any decomposition.

Co-assembling vaccines composed of a lipidated HER2-derived antigenic CH401 peptide and either a lipophilic adjuvant, Pam₃ CSK₄ , α-GalCer, or lipid A 506, were evaluated as breast cancer vaccine candidates. This vaccine design was aimed to inherit both antigen multivalency and antigen-specific immunostimulation properties, observed in reported self-adjuvanting vaccine candidates, by using self-assembly and adjuvant-conjugated antigens. Under vaccination concentrations, res

The antigenic trisaccharides, α‐gal epitope and H antigen, containing N ‐acetyl‐ d ‐glucosamine (GlcNAc) were synthesized using a diacetyl strategy, in which NHAc is tentatively converted to NAc 2 during oligosaccharide construction. Acetylation of NHAc in GlcNAc significantly improved the reactivity in glycosylation reactions. The diacetyl strategy allowed to achieve the efficient synthesis of α‐gal through a sequential one‐pot and one‐flow procedure. Meanwhile, H antigen was synthesized by ste

Asparagine-linked <i>N</i>-glycans on proteins have diverse structures, and their functions vary according to their structures. In recent years, it has become possible to obtain high quantities of <i>N</i>-glycans via isolation and chemical/enzymatic/chemoenzymatic synthesis. This has allowed for progress in the elucidation of <i>N</i>-glycan functions at the molecular level. Interaction analyses with lectins by glycan arrays or nuclear magnetic resonance (NMR) using various <i>N</i>-glycans hav

Amphidinol 3 (AM3), a membrane-active agent isolated from the dinoflagellate Amphidinium klebsii, consists of a long carbon chain containing 25 stereogenic centers. Although the absolute configuration of AM3 was determined by extensive NMR analysis and degradation of the natural product, the partial structure corresponding to the tetrahydropyran ring system was found to be antipodal to that of karlotoxin 2, a structurally related compound recently isolated from the dinoflagellate Karlodinium ven

We report a stepwise FLAG-tagging strategy for the purification of target proteins for bioactive metabolites. This method realizes the microscale purification and identification of target protein from as few as 1 x 10(5) differentiated cells. Using this method, we isolated and identified MetE as a cytosolic target protein of potassium isolespedezate, a metabolite controlling plant nyctinasty.

The chemical synthesis of a bisecting N-acetylglucosamine (GlcNAc)-containing N-glycan was achieved by a convergent synthetic route through [4+2] and [6+2] glycosylations. This synthetic route reduced the number of reaction steps, although the key glycosylations were challenging in terms of yields and selectivities owing to steric hindrance at the glycosylation site and a lack of neighboring group participation. The yields of these glycosylations were enhanced by stabilizing the oxocarbenium ion

The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc₂ to improve reactivity by preventing intermolecular hydrogen bonds. Another key was the glycosylation to the branched mannose in an ether solvent, which promoted the desired glycosylation by stabilizing the oxocarbenium ion intermediate. Furthermore, high α-selectivity of these glycosylation reactions was realized b

Individual interactions between glycans and their receptors are usually weak, although these weak interactions can combine to realize a strong interaction (multivalency). Such multivalency plays a crucial role in the recognition of host cells by pathogens. Glycodendrimers are useful materials for the reconstruction of this multivalent interaction. However, the introduction of a large number of glycans to a dendrimer core is fraught with difficulties. We herein synthesized antipathogenic glycoden

We report a promising cancer vaccine candidate comprising antigen/adjuvant-displaying enveloped viral replica as a novel vaccine platform. The artificial viral capsid, which consists of a self-assembled β-annulus peptide conjugated with an HER2-derived antigenic CH401 peptide, was enveloped within a lipid bilayer containing the lipidic adjuvant α-GalCer. The use of an artificial viral capsid as a scaffold enabled precise control of its size to ∼100 nm, which is generally considered to be optimal

Core fucosylation is catalyzed by α-1,6-fucosyltransferase (FUT8), which fucosylates the innermost GlcNAc of N-glycans. Given the association of FUT8 with various diseases, including cancer, selective FUT8 inhibitors applicable to in vivo or cell-based systems are highly sought-after. Herein, we report the discovery of a compound that selectively inhibits FUT8 in cell-based assays. High-throughput screening revealed a FUT8-inhibiting pharmacophore, and further structural optimization yielded an

Sialyl-Tn (STn), overexpressed on various tumors, has been investigated for its application in anti-cancer vaccine therapy. However, Theratope, an STn-based vaccine, failed in the phase III clinical trial due to poor immunogenicity and epitope suppression by the foreign carrier protein. We therefore developed a self-adjuvanting STn based-vaccine, a conjugate of clustered STn (triSTn) antigen, TLR1/2 ligand (Pam₃CSK₄), and T-helper (Th) cell epitope, and found that this thre