2009 Fiscal Year Final Research Report
De novo protein design using O-linked glycans
| Project/Area Number |
20710159
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Living organism molecular science
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| Research Institution | Hokkaido University |
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Principal Investigator |
FUJITANI Naoki Hokkaido University, 大学院・先端生命科学研究院, 特任助教 (10374191)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 生命化学 / 翻訳後修飾 / 立体構造デザイン / 核磁気共鳴 |
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| Research Abstract |
Glycopeptide mucins and IgA1 hinge region PSTPPTPSPSTPPTPSPS found in human were synthesized under microwave irradiation atmosphere and the three-dimensional structure analysis was performed.
In the case of IgA1 hinge, the glycopeptides with N-acetylgalactosamine (GalNAc) and core1 structure (Gal - GalNAc) were synthesized in the residue indicated by underlines.
As a result, 9 of proline formed an isomer of cis - trans out of a peptide without sugar, but a isomerizaton of cis - trans was drastically restrained to add a sugar chain modification (in particular, in the case of core1 structure), and that a structure with trans conformation exists mainly became clear. It was revealed that glycans on serine or threonine restrains an isomerizaton reaction of the proline which exists in the C-terminal side.
General solid phase synthesis of peptide is initiated from the C-termininal, but it is widely known that the yield decrease in the case of the first amino acid is proline because the peptide structure constructs a ring structure (diketopiperazin structure) in a deprotection reaction after the coupling. This is because proline forms a cis conformer, the knowledge obtained by IgA1 research, when I substitute for the 2nd amino acid in a sugar amino acid, proline is fixed on a trans conformer, and amino acid extension has occurred. A PCT application was performed about the case that a sugar chain has the effect which maintains the proline which exists next to the C-terminal as a trans conformer (cis-trans isomerizaton reaction slowed down.) and a Fmoc solid phase peptide synthesis method in the case of proline possesses in the C-terminal as a result of this research.
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[Journal Article] Functional Neoglycopeptides: Synthesis and Characterization of New Class MUC1 Glycoprotein Models Having Core 2-based O-Glycan and Complex-type N-Glycan Chains2009
Author(s)
Matsushita T., Sadamoto R., Ohyabu N., Nakata H., Fumoto M., Fujitani N., Takegawa Y., Sakamoto T., Kurogochi M., Hinou H., Shimizu H., Ito T., Naruchi K., Togame H., Takemoto H., Kondo H., Nishimura S. -I
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Journal Title
Biochemistry 48
Pages: 11117-11133
Peer Reviewed
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[Journal Article] Alterations in the glycoform of cisplatin-resistant human carcinoma cells are caused by defects in the endoplasmic reticulum-associated degradation system2008
Author(s)
Nakagawa H., Ohira M., Hayashi S., Abe S., Saito S., Nagahori N., Monde K., Shinohara Y., Fujitani N., Kondo H., Akiyama S. -I., Nakagawara A., Nishimura S. -I
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Journal Title
Cancer Lett 270
Pages: 295-301
Peer Reviewed
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