研究成果　-Reserch-


最新の成果

私たちの研究室では、単一構造のヒト型糖鎖をもつ糖タンパク質の化学合成を行っています。卵黄から単離したシアリル糖鎖を用いてペプチド固相合成、大腸菌発現法などを組み合わせてサイトカイン
類などの糖タンパク質を合成しました。

糖タンパク質を合成する際、糖ペプチドやペプチド鎖を連結するにはNative chemical ligationが簡便な方法ですが、合成するタンパク質が全てシステイン残基を持っているわけではありません。システインを用いて連結したのちシステインをセリンに変換する方法を見いだしました。

糖鎖が結合した糖ペプチドチオエステルはnative chemical ligation に必須の化合物です。Fmocペプチド固相合成を利用するチオエステル法の確立に成功しました。この方法をもちいて様々な糖タンパク質の合成を検討しています。

鶏卵はヒト型の糖鎖を多く含んでいます。この中からジシアリル複合型糖鎖を単離し、糖加水分解酵素を 用いて糖残基を１つづつ削除し、多様な構造の糖鎖を簡単に調製する方法を確立しました。


Selected papers concerned with glycoprotein and oligosaccharide syntheses.

  1. Y. Kajihara, Y. Suzuki, N. Yamamoto, K. Sasaki, T. Sakakibara, L. R. Juneja; Prompt chemo-enzymatic synthesis of diverse complex-type oligosaccharides and its application to the solid-phase synthesis of a glycopeptide with Asn-linked sialyl-undeca- and asialo-nona-saccharides. Chem. Eur. J. (2004), 10(4), 971-985.

  2. N. Yamamoto, Y. Tanabe, R. Okamoto, P. E. Dawson, Y. Kajihara; Chemical Synthesis of a Glycoprotein Having an Intact Human Complex-Type Sialyloligosaccharide under the Boc and Fmoc Synthetic Strategies. J. Am. Chem. Soc. (2008), 130(2), 501-510.

  3. K. Hirano, D. Macmillan, K. Tezuka, T. Tsuji, Y. Kajihara; Design and Synthesis of Homogeneous Erythropoietin Analogue with Two Human Complex-Type Sialyloligosaccharides: Combined Use of Chemical and Bacterial Protein Expression Methods. Angew. Chem. Int. Ed. (2009), 48, 9557-9560.

  4. R. Okamoto, Y. Kajihara; Uncovering latent ligation site for glycopeptide synthesis. Angew. Chem. Int. Ed. (2008), 47(29), 5402-5406.

  5. N. Yamamoto, Y. Ohmori, T. Sakakibara, K. Sasaki, L. R. Juneja, Y. Kajihara; Solid-phase synthesis of sialylglycopeptides through selective esterification of the sialic acid residues of an Asn-linked complex-type sialyloligosaccharide. Angew. Chem. Int. Ed. (2003), 42(22), 2537-2540.

  6. T. Miyazaki, H. Sato, T. Sakakibara, Y. Kajihara; An Approach to the Precise Chemoenzymatic Synthesis of 13C-Labeled Sialyloligosaccharide on an Intact Glycoprotein: A Novel One-Pot [3-13C]-Labeling Method for Sialic Acid Analogues by Control of the Reversible Aldolase Reaction, Enzymatic Synthesis of [3-13C]-NeuAc- α -(2→ 3)-[U-13C]-Gal-β -(1→ 4)-GlcNAc-β - Sequence onto Glycoprotein, and Its Conformational Analysis by Developed NMR Techniques. J. Am. Chem. Soc. (2000), 122(24), 5678-5694.　

  7. T. Miyazaki, T. Sakakibara, H. Sato, Y. Kajihara; Chemoenzymic Synthesis of the 9-Deoxy-9-fluoro-[3-13C]-NeuAc- α -(2→ 6)-[U-13C]-β -Gal Sequence on an Intact Glycoprotein. J. Am. Chem. Soc. (1999), 121(6), 1411-1412.

  8. Y. Kajihara, T. Ebata, H. Kodama; Synthesis of immobilized CMP-sialic acids and their enzymic transfer with sialyltransferase. Angew. Chem. Int. Ed. (1998), 37(22), 3166-3169.

  9. R. Okamoto, S. Souma, Y. Kajihara; Efficient Substitution Reaction from Cysteine to the Serine Residue of Glycosylated Polypeptide: Repetitive Peptide Segment Ligation Strategy and the Synthesis of Glycosylated Tetracontapeptide Having Acid Labile Sialyl-TN Antigens. J. Org. Chem. (2009), 74 , 2494 –2501.

  10. R. Okamoto, S. Souma, Y. Kajihara; Efficient Synthesis of MUC4 Sialylglycopeptide through the New Sialylation Using 5-Acetamido-Neuraminamide Donors. J. Org. Chem. (2008), 73(9), 3460-3466.

  11. N. Yamamoto, A. Takayanagi, A. Yoshino, T. Sakakibara, Y. Kajihara; An approach for a synthesis of asparagine-linked sialylglycopeptides having intact and homogeneous complex-type undecadisialyloligosaccharides. Chem. Eur. J. (2007), 13(2), 613-625.

  12. Y. Kajihara, T. Yamamoto, H. Nagae, M. Nakashizuka, T. Sakakibara, I. Terada; A Novel α -2,6-Sialyltransferase: Transfer of Sialic Acid to Fucosyl and Sialyl Trisaccharides. J. Org. Chem. (1996), 61(24), 8632-8635.

  13. Y. Kajihara, T. Ebata, K. Koseki, H. Kodama, H. Matsushita, H. Hashimoto; Efficient Chemical Synthesis of CMP-Neu5Ac and CMP-(Neu5Ac α 2→ 8Neu5Ac). J. Org. Chem. (1995), 60(17), 5732-5735.

  14. Y. Kajihara, N. Yamamoto, R. Okamoto, K. Hirano, T. Murase. Chemical synthesis of homogeneous glycopeptides and glycoproteins. Chemical Record, 2010, 10, 80-100.

  15. T. Murase, Y. Kajihara, Synthesis of the glycosylated polypeptide chain of an inducible costimulator on T-cells, Carbohydr. Res. (2010), 345(10), 1324-1330.

  16. K. Hirano, Y. Kajihara, Synthesis of Heavily Glycosylated Peptide α-Thioester, J. Carbohydr.Chem. (2010), 29(2), 84-91.

  17. T. Murase, T. Tsuji, Y. Kajihara; Efficient and systematic synthesis of a small glycoconjugate library having human complex type oligosaccharides　Carbohydr. Res., 344, (2009), 762-770.

  18. Y. Kajihara, A. Yoshihara, K. Hirano, N. Yamamoto; Convenient synthesis of a sialylglycopeptide-thioester having an intact and homogeneous complex-type disialyl-oligosaccharide. Carbohydr. Res. (2006), 341(10), 1333-1340.

  19. K. Fukae, N. Yamamoto, Y. Hatakeyama, Y. Kajihara; Chemoenzymatic synthesis of diverse asparagine-linked α -(2,3)-sialyloligosaccharides. Glycoconjugate J. (2004), 21(5), 243-250.