Earticle

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영어

CD22 (siglec-2) is an accessory molecule of the B-cell receptor complex (BCR) that exertsnegative effects on receptor signaling. It is also well-documented that CD22 is a regulatoryprotein that sets a threshold for immune responses. The carbohydrate ligand recognized byCD22 is the sequence Neuα(2,6)Galβ(1,4)GlcNAc found on both neighboringglycoconjugate of the same cell (cis ligand) and on other cells that interact with B cells (transligands). Recently, we have reported that the C-9 amido derivative of sialic acid (GSC718;9-(4’-hydroxy-4-biphenyl)acetamido-9-deoxy-Neu5Gc-OBn) show a potent affinity andselectivity for CD22 than other siglecs such as MAG [1]. Moreover, the compoundpromoted the proliferation of B cells in vitro. As next step of our investigation, we intend toreinforce the promoting activity of GSC718 for B cell growth by chemical modification.Herein, we report the efficient synthesis of GSC718 analogs which have varied aglyconmoieties. To achieve the comprehensive synthesis of GSC718 analogs having varied aglycons, wereexamined every synthetic process to obtain a fine target compound. In case of thesialoside synthesis, the most time-consuming and troublesome process is thechromatographic separation of α-sialoside from other byproducts such as β−isomer, 2,3-enederivative etc. after glycosylation reaction with aglycon part. To improve this process, weemployed 1,5-lactam formation as the key step for separation because the lactam formation isknown to proceed only in α-sialoside [2]. At the beginning of the synthesis of targetmolecules, we synthesized a suitably modified sialic acid donor in good yields. Then, thesialyl donor was reacted with various 2-substituted-ethanols to give the mixtures of α- and β-glycosides and 2,3-ene derivative, which were subsequently advanced to 1,5-lactamformation. As we anticipated, 1,5-lactamized α-sialosides became isolable from themixtures due to its different polarity from the other byproducts. Finally, the obtained 1,5-lactamized silaosides were successfully converted into target structures via reaction sequenceincluding C9-midification with biphenyl amide group, lactam opening and globaldeprotection. The synthesized analogs were advanced to biological assay using B cells. In
this poster presentation, we will also discuss the structure-activity relationships of thesynthesized analogs. [1] H. H. M. Abdu-Allah et al, Bioorg. Med. Chem. Lett. 2011, 19, 1966-1971. [2] H. Tanaka et al, Tetrahedron Lett. 2009, 50, 4478-4481.

저자

• Yuki Sugamuna [ Department of Applied Bioorganic Chemistry Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan. ]
• Naoko Matsubara [ Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. ]
• Yuki Iwayama [ Department of Applied Bioorganic Chemistry Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan. Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan. ]
• Akiharu Ueki [ Department of Applied Bioorganic Chemistry Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan. Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan. ]
• Akihiro Imamura [ Department of Applied Bioorganic Chemistry Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan. Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan. ]
• Hiromune Ando [ Department of Applied Bioorganic Chemistry Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan. Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan. ]
• Takeshi Tsubata [ Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. ]
• Hideharu Ishida [ Department of Applied Bioorganic Chemistry Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan. ]
• Makoto Kiso [ Department of Applied Bioorganic Chemistry Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan. Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan. ]

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표지보기 관심저널 등록

• 간행물명

  한국당과학회 학술대회

• 간기

  연간

• 수록기간

  2006~2022

• 십진분류

  KDC 517 DDC 614