Development of Glyco-Nanomaterials Tissue Engineering and Infectious Diseases

糖基纳米材料组织工程与传染病研究进展

基本信息

批准号：
14350486
负责人：
KOBAYASHI Kazukiyo
金额：
$ 10.56万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

(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

（1）使用易感脂肪酶催化的反应制备糖缀合物聚合物。在初级羟基中选择性地酯化了海藻糖（GLCα1-1αGLC）和Gal-Type tyhalose（GALα1-1-1αGLC）的非还原二糖。通过自由基引发剂聚合所得的糖乙烯酯。糖缀合物聚合物根据携带糖结构显示生物学活性。尤其是，携带gal型海洛糖的聚合物表明对志贺毒素1的非抑制活性。（2）微孔碳水化合物的显示器是由糖缀合物聚合物自组装在硅上的疏水模板上的自我组装。这种方法利用了SI底物上的ODS-SAM的光刻造影和随后的选择性自组装在疏水区域上的选择性自组装。通过分子识别在碳水解底物上通过分子识别的蛋白微图案也成功了。（3）6-硫代基因的几何形状接近N-乙酰基神经氨酸（NEU5AC）的蛋白质几何形状，可以用作简单的NEU5AC模拟物质和医学应用中的高潜力。使用P-硝基苯基（PNP）3-，4-和6-硫酸-βDGLCNAC和6-硫酸-BDGLC的神经辛酶抑制测定法证明了这一假设，其中仅发现PNP 6-Sulfo-βDGLCNAC2A才能显示出实质性的活性。 N-乙酰基-6-硫酸-B-D-d-葡萄糖酰胺（6-硫酸-GLCNAC 1）具有与N-乙酰基神经氨酸酸（NEU5AC 2）和2-脱氧-2,3-脱氧脱氧基乙基乙酰氨基酸（NEU5AC2EN 3）的影响（neu5ac2en 3）的影响（neu5AC2EN 3）的影响（neu5AC 2）在n neu5Ac neu n neus a n n n n s sialsied（neu5AC 2）与n-乙酰神经氨酸酸（NEU5AC 2）相关（neu5ac 2 A/MEMPHIS/1/71 H3N2）。事实证明，PNP6-Sulfo-GlCNAC 1A表现出很大的活性以抑制唾液酸酶（IC_ <50> =2.8μm）。当将1A的PNP组转换为p-乙酰氨基苯基一号5（IC_ <50> = 30 mm）或用1-萘基6（IC_ <50> =10μm）或N-丙基一个8（IC_ <50> =11μm）（5）碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 碳水化合物 - 盐水氢液含量，将其增强近100倍。使用表面压力区（P-A）等温线和表面等离子体共振（SPR）研究了沿聚苯乙烯链的Langmuir单层和聚集的GG3三糖。进行了GM3-GG3相互作用的SPR研究，以定量地估计相互作用的亲和力常数和特异性。 Pn（GG3）在GM3单层上被吸附到GM3单层上，具有k_a的明显亲和力常数= 2.5 x 10^6 m- <-1>。我们发现，GM3中的N-乙酰基神经氨酸的NHAC组和GG3中的GALNAC在GM3-GG3相互作用中起着重要作用，并且PN（GG3）不仅识别GM3的某些指定部分，而且识别TrisacCharide的某些指定部分。较少的