2004 Fiscal Year Final Research Report Summary
Development of Glyco-Nanomaterials Tissue Engineering and Infectious Diseases
| Project/Area Number |
14350486
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
高分子合成
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
KOBAYASHI Kazukiyo Nagoya University, Graduate School of Engineering, Professor, 工学研究科, 教授 (10023483)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Yoshihiro Nagoya University, Graduate School of Engineering, Associate Professor, 工学研究科, 助教授 (80183896)
MIURA Yoshiko Nagoya University, Graduate School of Engineering, Assistant Professor, 工学研究科, 助手 (00335069)
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Keywords | Glycoscience / Biomaterials / Tissue Engineering / Scaffold / Biodegradable / Molecular Recognition / Cell Culture / Infectious Diseases |
|---|
| Research Abstract |
(1)Glycoconjugate polymers were prepared using a facile lipase catalyzed reaction. Non-reducing disaccharides of trehalose (Glcα1-1αGlc) and Gal-type trehalose (Galα1-1αGlc) were selectively esterified at the primary hydroxyl groups. The resultant saccharide vinyl esters were polymerized by a radical initiator. The glycoconjugate polymers showed the biological activities based on the carrying saccharide structures. Especially, the polymer carrying Gal-type trehalose showed the inihibition activity to Shiga toxin-1.
(2)Micropatterned Carbohydrate Displays have been prepared by Self-Assembly of Glycoconjugate Polymers on Hydrophobic Templates on Silicon. This method exploited the hydrophobic-hydrophilic microfabrication by photolithography of ODS-SAM on Si substrates and the subsequent selective self-assembly of glycoconjugate polymers onto the hydrophobic regions. Protein micropatterning by molecular recognition on the carbohydrate substrates was also successful.
(3)6-SulfodGlcNAc with a
… More
molecular geometry close to that of N-acetylneuraminic acid (Neu5Ac) was hypothesized to serve as a simple Neu5Ac mimic possessing high potential in biochemical and medicinal applications. The hypothesis was evidenced with a neuraminidase inhibition assay using p-nitrophenyl(pNP) 3-,4-,and 6-sulfo-βdGlcNAc and 6-sulfo-bdGlc, in which only pNP 6-sulfo-βdGlcNAc 2a was found to show substantial activity.
(4)Biological activity of N-acetyl-6-sulfo-b-D-glucosaminides (6-sulfo-GlcNAc 1) having a structural homology to N-acetylneuraminic acid (Neu5Ac 2) and 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en 3) was examined in terms of inhibitory activity against influenza virus sialidase (influenza A/Memphis/1/71 H3N2). pNP6-Sulfo-GlcNAc 1a was proved to show substantial activity to inhibit the virus sialidase (IC_<50>=2.8 μM). The activity was enhanced by a factor of nearly 100 times when the pNP group of 1a was converted to p-acetamidophenyl one 5 (IC_<50>=30 mM) or replaced with 1-naphthyl 6 (IC_<50>=10 μM) or n-propyl one 8 (IC_<50>=11 μM).
(5)Carbohydrate-carbohydrate interactions between clustered GM3 on the Langmuir monolayer and clustered Gg3 trisaccharide along a polystyrene chain were investigated using surface pressure-area (p-A) isotherms and surface plasmon resonance (SPR). SPR studies of the GM3-Gg3 interaction were carried out to estimate the affinity constant and specificity of the interaction quantitatively. PN(Gg3) was adsorbed onto the GM3 monolayer strongly and specifically with an apparent affinity constant of K_a=2.5 x 10^6 M-<-1>. We found that the NHAc groups of N-acetylneuraminic acid in GM3 and of GalNAc in Gg3 play an important role in the GM3-Gg3 interaction and that PN(Gg3) recognizes not only some specified portions of GM3 but also the trisaccharide as a whole. Less
|
