Papers - Fujimoto Yukari

Site-specific effect of polar functional group-modification in lipids of TLR2 ligands for modulating the ligand immunostimulatory activity.

Arai, Y., Inuki, S., Fujimoto, Y.

Bioorg Med Chem Lett. (Bioorganic and Medicinal Chemistry Letters)  28 ( 9 ) 1638 - 1641 2018

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0960894X

　View Summary

© 2018 Elsevier Ltd Toll-like receptor 2 (TLR2), a member of the TLR innate immune receptor family, recognizes lipoproteins from bacteria and modulates the immune response by inducing the expression of various cytokines. TLR2 has a large hydrophobic pocket that recognizes long fatty acyl groups on TLR2 ligands. However, few studies have focused on the property of the hydrophobic TLR2 pocket. Based on the X-ray crystal structure of TLR2, small polar regions were found in the hydrophobic TLR2 pocket. Interactions between the polar residues and ligands were explored here by designing and synthesizing a Pam2CSK4 derivative of the TLR2 ligands, containing an amide group within the lipid moiety. We evaluated the binding affinities and immunomodulatory activities of these ligands. Results suggested that the amide groups in the lipid chain interacted with the polar residues in the hydrophobic lipid-binding pocket of TLR2.

• Access to Document (DOI)

Time-lapse monitoring of TLR2 ligand internalization with newly developed fluorescent probes.

Arai, Y., Yokoyama, K., Kawahara, Y., Feng, Q., Ohta, I., Shimoyama, A., Inuki, S., Fukase, K., Kabayama, K., Fujimoto, Y.

Org. Biomol. Chem. (Organic and Biomolecular Chemistry)  16 ( 20 ) 3824 - 3830 2018

Research paper (scientific journal), Joint Work,  ISSN  14770520

　View Summary

© 2018 The Royal Society of Chemistry. As a mammalian toll-like receptor family member protein, TLR2 recognizes lipoproteins from bacteria and modulates the immune response by inducing the expression of various cytokines. We have developed fluorescence-labeled TLR2 ligands with either hydrophilic or hydrophobic fluorescence groups. The labeled ligands maintained the inflammatory IL-6 induction activity and enabled us to observe the internalization and colocalization of the TLR2 ligands using live-cell imaging. The time-lapse monitoring in the live-cell imaging of the fluorescence-labeled TLR2 ligand showed that TLR2/CD14 expression in the host cells enhanced the internalization of TLR2 ligand molecules.

• Access to Document (DOI)

The second and third amino acids of Pam2 lipopeptides key for the proliferation of cytotoxic T cells.

Takeda, Y., Azuma, M., Hatsugai, R., Fujimoto, Y., Hashimoto, M., Fukase, K., Matsumoto, M., Seya, T.

Innate Immunity (Innate Immunity)  24 ( 5 ) 323 - 331 2018

Research paper (scientific journal), Joint Work,  ISSN  17534259

　View Summary

© The Author(s) 2018. The TLR2 agonist, dipalmitoyl lipopeptide (Pam2LP), has been used as an immune adjuvant without much success. Pam2LP is recognised by TLR2/6 receptors in humans and in mice. This study examined the proliferative activity of cytotoxic T lymphocytes (CTL) using mouse Ag-presenting dendritic cells (DCs) and OT-I assay system, where a library of synthetic Pam2LP was utilised from the Staphylococcus aureus database. Ag-specific CTL expansion and IFN-γ levels largely depended on the Pam2LP peptide sequence. The first Aa is cysteine (Cys), which has an active SH residue to bridge fatty acids, and the second and third Aa are hydrophilic or non-polar. The sequence structurally adapted to the residual constitution of the reported TLR2/6 pocket. The inactive sequence contained proline or leucine/isoleucine after the first Cys. Notably, no direct activation of OT-I cells was detected without DCs by stimulation with the active Pam2LP having the Cys-Ser sequence. MyD88, but not TICAM-1 or IFN pathways, in DCs participates in DC maturation characterised by upregulation of CD40, CD80 and CD86. Hence, the active Pam2LPs appear suitable for dimeric TLR2/6 on DCs, resulting in induction of DC maturation.

• Access to Document (DOI)

Employing BINOL-phosphoroselenoyl chloride for selective inositol phosphorylation and chemical synthesis of glycosyl inositol phospholipid from Entamoeba histolytica.

Aiba, T., Suehara, S., Choy, S.-L., Maekawa, Y., Lotter, H., Murai, T., Inuki, S., Fukase, K., Fujimoto, Y.

Chem. Eur. J. 23   8304 - 8308 2017.04

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Formal Total Synthesis of L-Ossamine via Decarboxylative Functionalization Using Visible-Light-Mediated Photoredox Catalysisin a Flow System

Inuki, S., Sato, K., Fukuyama, T., Ryu, I., Fujimoto, Y.

J. Org. Chem. 82 ( 2 ) 1248 - 1253 2017.01

Research paper (scientific journal), Accepted

• Access to Document (DOI)

Synthesis of Peptidoglycan Fragments from Enterococcus faecalis with Fmoc-Strategy for Glycan Elongation.

Wang, N., Hasegawa, H., Huang, CY., Fukase, K., Fujimoto, Y.

Chem Asian J. 12 ( 1 ) 27 - 30 2017.01

Research paper (scientific journal)

• Access to Document (DOI)

Convergent Synthesis of Digalactosyl Diacylglycerols.

Inuki, S., Kishi, J., Kashiwabara, E., Aiba, T., Fujimoto, Y.

Org. Lett. 19   6482 2017

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Funiculosin variants and phosphorylated derivatives promote innate immune responses via the Toll-like receptor 4/myeloid differentiation factor-2 complex.

Okamoto, N., Mizote, K., Honda, H., Saeki, A., Watanabe, Y., Yamaguchi-Miyamoto, T., Fukui, R., Tanimura, N., Motoi, Y., Akashi-Takamura, S., Kato, T., Fujishita, S., Kimura, T., Ohto, U., Shimizu, T., Hirokawa, T., Miyake, K., Fukase, K.,Fujimoto, Y., Nagai, Y., Takatsu, K.

J. Biol. Chem. 292 ( 37 ) 15378 - 15394 2017

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

A Comprehensive Study of the Interaction between Peptidoglycan Fragments and the Extracellular Domain of Mycobacterium tuberculosis Ser/Thr Kinase PknB.

Wang, Q., Marchetti, R., Prisic, S., Ishii, K., Arai, Y., Ohta, I., Inuki, S., Uchiyama, S., Silipo, A., Molinaro, A., Husson, R. N., Fukase, K.,. Fujimoto, Y.

ChemBioChem 18   2094 - 2098 2017

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Chemical Synthesis of D-glycero-D-manno-Heptose 1,7-Bisphosphate and Evaluation of Its Ability to Modulate NF-κB Activation.

Inuki, S., Aiba, T., Kawakami, S., Akiyama, T., Inoue, J. I., Fujimoto, Y.

Org. Lett. 19 ( 12 ) 3079 - 3082 2017

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Total Synthesis of Cardiolipins Containing Chiral Cyclopropane Fatty Acids.

Inuki, S., Ohta, I., Ishibashi, S., Takamatsu, M., Fukase, K., Fujimoto, Y.

J. Org. Chem. 82 ( 15 ) 7832 - 7838 2017

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Synthetic analogs of a protozoan glycolipid designed to combat intracellular Leishmania infection.

Choy, S. L., Bernin, H., Aiba, T., Bifeld, E., Lender, S. C., Mühlenpfordt, M., Noll, J., Eick, J., Marggraff, C., Niss, H., Roldán, N. G., Tanaka, S., Kitamura, M., Fukase, K., Clos, J., Tannich, E., Fujimoto, Y., Lotter, H.

Sci. Rep. 7   9472 2017

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Characterization of a novel D-glycero-D-talo-oct-2-ulosonic acid-substituted lipid a moiety in the lipopolysaccharide produced by the acetic acid bacterium Acetobacter pasteurianus NBRC 3283.

Hashimoto, M., Ozono, M., Furuyashiki, M., Baba, R., Hashiguchi, S., Suda, Y., Fukase, K., Fujimoto, Y.

J. Biol. Chem. 291 ( 40 ) 21184 - 21194 2016.09

Research paper (scientific journal), Accepted

• Access to Document (DOI)

Synthesis of characteristic Mycobacterium peptidoglycan (PGN) fragments utilizing with chemoenzymatic preparation of meso-diaminopimelic acid (DAP), and their modulation of innate immune responses

Wang, Q., Matsuo, Y., Pradipta, A. R., Inohara, N., Fujimoto, Y., Fukase, K.

Org. Biomol. Chem. 14   1013 - 1023 2016.01

Research paper (scientific journal), Accepted

• Access to Document (DOI)

Efficient synthesis of (‒)-hanishin, (‒)-longamide B, and (‒)-longamide B Methyl Ester via piperazinone formation with 1,2-cyclic sulfamidates

Shiokawa, Z., Inuki, S., Fukase, K., Fujimoto, Y.

Synlett 27 ( 4 ) 616 - 620 2016.01

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Peptidoglycan Microarray as A Novel Tool to Explore Protein-Ligand Recognition

Wang, N., Hirata, A., Nokihara, K., Fukase, K., Fujimoto, Y.

Biopolymers 106 ( 4 ) 422 - 429 2016

Research paper (scientific journal)

• Access to Document (DOI)

Regioselective Phosphorylation of myo-Inositol with BINOL-Derived Phosphoramidites, and Its Application for Protozoan Lysophosphatidylinositol

Aiba, T., Sato, M., Umegaki, D., Iwasaki, T., Kambe, N., Fukase, K. Fujimoto, Y.

Org. Biomol. Chem. 14   6672 - 6675 2016

Research paper (scientific journal), Accepted

• Access to Document (DOI)

Discovery of a Novel Scaffold as an Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid, Longamide B.

Shiokawa, Z., Kashiwabara, E., Yoshidome, D., Fukase, K., Inuki, S., Fujimoto, Y.

ChemMedChem. 11 ( 24 ) 2682 - 2689 2016

Research paper (scientific journal), Accepted

• Access to Document (DOI)

Visible-light-mediated decarboxylative benzoyloxylation of β-hydroxy amino acids and its application to synthesis of functional 1,2-amino alcohol derivatives

Inuki, S., Sato, K., Fujimoto, Y.

Tetrahedron Lett. 56   5787 - 5790 2015.09

Research paper (scientific journal), Joint Work, Accepted

• Access to Document (DOI)

Synthesis and Biological Activity of Inositol Phospholipid as NKT Cell Modulator.

Aiba, T., Suehara, S., Bernin, H., Lotter, H., Inuki, S., Fukase, K., Fujimoto, Y.

Glycoconjugate J. 32   301 2015

Research paper (international conference proceedings), Joint Work