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1 pp. D- Frontier Science in Amino Acid and Protein Research L L D D-D-Asp Asp D Asp D L D L D L D L D L D L-D- Racemization of aspartyl residues of proteins in age-related disease Noriko FujiiResearch Reactor Institute, Kyoto University, Kumatori, Sennan, Osaka, Japan Yuichi KajiDepartment of Ophthalmology, Tsukuba University Institute of Clinical Medicine, Tennoudai, Tsukuba, Ibaraki, Japan LD- L- LD- D-L- L- D- L- L- L- L- L- L D D- D-Asp

2 D- D- αa- αb- D-Asp D-Asp D-Asp Asp, Asp Asp, Asp D-Asp D-Asp D-Asp β- D-Asp β- D-Ser D-Asp D- D-Asp D- D-Asp D-Asp Asp D-Asp α- αa- αb- αβγ- βγ- D-Asp Asp, Asp, Asp Ser, D-Asp D-Asp C D-Asp D-Asp Asp D-Asp D-Asp αaαb- Asp Asp AspDL αa Asp- β α Ser- αa Asp- β α Ala- αb Asp- β α Leu- αb Asp- β α Thr- αa-αb- kda αa- Asp AsnαB- Asp Asn AspAsn D αa-αb- HPLC AspAsn AspAsn DL αa-αb- Asp DL αa- Asp-Asp- αb- Asp-Asp- D AspAsn αa- Asp- DL Asp- DL D L Asp DL αa- αa-αb-l-asp D-Asp α β β-asp Asp D Asp L D α β L-α-

3 Asp Asp C α β D- D-α-Asp D-β-Asp L- L-α-AspL-β-Asp D- Asp Asp L D H Asp Asp αa- Asp-Asp- Ser-Ala- Asp Asp-Asp- αb- Asp- Asp- Asp αb- Asp-GlyAsn-Gly Asp Asp αa- Asp-Asp- DL I D- Asp

4 2 9 0 生化学 第8 0巻 第 4 号 図2 老人の顔の皮膚に存在する D-β-Asp 含有タンパク質 赤色部位 図3 瞼裂斑における D-β-Asp 含有タンパク質の局在 図4 加齢性黄斑変性における D-β-Asp 含有タンパク質の局在

5 αa- Asp- αa- Asp- D-β-Asp αa- Asp- D-β-Asp D-β-Asp Asp D-β-Asp D-β-Asp D-β-Asp D-β-Asp D-β-Asp kda D-β-Asp D-β-Asp spheroid degeneration D-β-Asp D-β-Asp D-β-Asp D-β-Asp D- D- L- Asp α β D-Asp α- β- β β D- β- D-Asp D-D-Ser Roher β- Asp-Asp-Asp- L-β-Asp D-Asp β- Asp- D β-β L β β- Asp L-β-Asp Asp Ser- D β- Ser- β-

6 D- D-Asp Masuda D-Asp I C CTx CTxAHDGGR Asp- CTx Asp- D-Asp Asp D-Asp Asp Asp Asp Asp A Asp A Asp GVADAAAAREGDPSSSAGADEGVR Asp DL Asp Asp Asp E kcalmol k GVADAAAA A- REGDPSSS A- AGADEGVR EkAsp Y Asp DL Y Asp DL Asp Asp Asp D L Asp Asp αa- αb- Asp D-Asp L-β-Asp PIMTprotein L- isoaspartyl methyltransferase D-α-Asp DAEPD-aspartyl endopeptidase Fujii, N., Satoh, K., Harada, K., & Ishibashi, Y.J. Biochem.,,. Fujii, N., Ishibashi, Y., Satoh, K., Fujino, M., & Harada, K. Biochim. Biophys. Acta,,. Kaji, Y., Oshika, T., Takazawa, Y., Fukayama, M., Takata, T., &Fujii, N.Invest. Ophthalmol. Vis. Sci.,,. Fisher, G.H., Garcia, N.M., Payan, I.L., Cadilla-Perezrios, R., Sheremata, W.A., & Man, E.H.Biochem. Biophys. Res. Commun.,,. Roher, A.E., Lowenson, J.D., Clarke, S., Wolkow, C., Wang,

7 R., Cotter, R.J., Reardon, I.M., Zurcher-Neely, H.A., Heinrikson, R.L., Ball, M.J., & Greenberg, B.D. J. Biol. Chem.,,. Kaneko, I., Yamada, N., Sakuraba, Y., Kamenosono, M., & Tutumi, S.J. Neurochem.,,. Fujii, N., Tajima, S., Tanaka, N., Fujimoto, N., Takata, T., & Shimo-Oka, T.Biochem. Biophys. Res. Commun.,,. Masuda, W., Nouso, C., Kitamura, C., Terashita, M., & Noguchi, T.Arch. Oral. Biol.,. Ritz, S., Turzynski, A., Schutz, H.W., Hollmann, A., & Rochholz, G.Forensic Sci. Int.,,. Cloos, P.A. & Fledelius, C.Biochem. J.,,. Powell, J.T., Vine, N., & Crossman, M.Atherosclerosis,,. Ritz-Timme, S., Laumeier, I., & Collins, M.Int. J. Legal Med.,,. Fujii, N., Harada, K., Momose, Y., Ishii, N., & Akaboshi, M. Biochem. Biophys. Res. Commun.,,. Fujii, N., Shimo-oka, T., Ogiso, M., Momose, Y., Kodama, M., & Akaboshi, M.,Mol. Vis.,,. Tomiyama, T., Asano, S., Furiya, Y., Shirasawa, T., Endo, N., &Mori,H.J. Biol. Chem.,,. Shimizu, T., Fukuda, H., Murayama, S., Izumiyama, N., & Shirasawa, T.Neurosci. Res.,,. Kuge, K., Fujii, N., Miura, Y., Tajima, S., & Saito, T. Amino Acids,,. McFadden, P.N. & Clarke, S.Proc. Natl. Acad. Sci. USA,,. Kinouchi, T., Ishiura, S., Mabuchi, Y., Urakami-Manaka, Y., Nishio, H., Nishiuchi, Y., Tsunemi, M., Takada, K., Watanabe, M., Ikeda, M., Matsui, H., Tomioka, S., Kawahara, H., Hamamoto, T., Suzuki, K., & Kagawa, Y.Biochem. Biophys. Res. Commun.,,.

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