Study on the structure and function of glycans in target proteins for moving toward individualized medicine using antibody drugs
| Project/Area Number |
26293037
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Yokohama City University (2015-2016)
National Institute of Health Sciences (2014) |
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Principal Investigator |
Kawasaki Nana 横浜市立大学, 生命医科学研究科, 教授 (20186167)
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| Co-Investigator(Kenkyū-buntansha) |
小川 久美子 国立医薬品食品衛生研究所, 病理部, 部長 (70254282)
多田 稔 国立医薬品食品衛生研究所, 生物薬品部, 室長 (50506954)
石井 明子 国立医薬品食品衛生研究所, 生物薬品部, 室長 (50291117)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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| Keywords | 糖鎖 / 質量分析 / EGF受容体 / 抗体医薬品 / 個別化医療 / 薬効 / 体内動態 |
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| Outline of Final Research Achievements |
For individualized medicine using monoclonal antibody drugs (mAbs)， it is important to clarify the diversity of target molecules for mAbs and the relationship between the diversity and efficacy and safety of mAb products. To elucidate the glycan diversity on target proteins for mAbs， we developed an analytical method for the site-specific glycosylation of membrane proteins; this method comprised the extraction of target proteins from the membrane fraction by immunoprecipitation with mAbs， trypsin digestion， glycopeptide enrichment by acetone precipitation， and LC/MS. Using the method， we successfully demonstrated the glycosylation at 5 sites of EGFR in A431 cells. It was suggested that Asn 528 is attached to unique glycans bearing both 7-9 GlcNAc and 2-6 Fuc residues. We also showed the site-specific glycosylation of the Fc gamma receptor IIIb expressed in Baby hamster kidney cells and in human serum.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Characterization of Glycoproteins Expressing the Blood Group H Type 1 Epitope on Human Induced Pluripotent Stem (hiPS) Cells2016
Author(s)
Nakao, H., Matsumoto, S., Nagai, Y., Kojima, A., Toyoda, H., Hashii, N., Takakura, D., Kawasaki, N., Yamaguchi, T., Kawabata, K., Kawasaki, N., Kawasaki, T.
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Journal Title
Glycoconjugate J
Volume: 19
Issue: 6
Pages: 1-9
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis.2016
Author(s)
Ohmi Y, Ise W, Harazono A, Takakura D, Fukuyama H, Baba Y, Narazaki M, Shoda H, Takahashi N, Ohkawa Y, Ji S, Sugiyama F, Fujio K, Kumanogoh A, Yamamoto K, Kawasaki N, Kurosaki T, Takahashi Y, Furukawa K.
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Journal Title
Nature Communications
Volume: in press
Issue: 1
Pages: 11205-11205
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines. HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study.2015
Author(s)
Ito H,Kaji H,Togayachi A,Azadi P,Ishihara M,Geyer R, Galuska C,Geyer H,Kakehi K,Kinoshita M,Karlsson NG,Jin C,Kato K,Yagi H,Kondo S,Kawasaki N,Hashii N,Kolarich D,Stavenhagen K,Packer NH,Thaysen-Andersen M,Nakano M,Taniguchi N,Kurimoto A,Wada Y,Tajiri M,Yang P,Cao W,Li H,Rudd PM,Narimatsu H.
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Journal Title
Glycoconjugate J
Volume: Oct 28
Related Report
Peer Reviewed / Open Access
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