Development of Glyco-Nanomaterials Tissue Engineering and Infectious Diseases

(1)利用简单的脂肪酶催化反应制备了糖共轭聚合物。非还原海藻糖二糖(Glcα1-1αGlc)和半乳糖型海藻糖(Gal型α1-1αGlc)选择性地在伯羟基酯化。合成的糖基乙烯基酯由自由基引发剂聚合。糖共轭聚合物是基于载体糖结构而显示出生物活性的聚合物。特别是半乳糖型海藻糖聚合物对志贺毒素-1具有抑制活性。(2)通过糖共轭聚合物在硅表面的疏水模板自组装，制备了糖链微图案化的碳水化合物显示器。这种方法利用了在硅衬底上光刻ODS-SAM和随后糖共轭聚合物在疏水区域选择性自组装的疏水-亲水微细加工。通过分子识别在碳水化合物底物上进行蛋白质微图案化也是成功的。(3)带有…的6-磺酸-GlcNAc更多接近N-乙酰神经氨酸(Neu5Ac)的分子构型被认为是一种简单的Neu5Ac模拟物，具有很高的生物化学和医药应用潜力。用对硝基苯基3-，4-和6-磺酸-βdGlcNAc和6-磺酸-bdGlc进行的神经氨酸酶抑制实验证实了这一假说，其中只有PNP 6-磺酸-βdGlcNAc 2a显示出显著的活性。(4)N-乙酰-6-磺酸-b-D-氨基葡萄糖胺(6-磺基-GlcNAc 1)的生物活性与N-乙酰神经氨酸(Neu5Ac 2)和2-脱氧-2，3-脱氢-N-乙酰神经氨酸(Neu5Ac2en 3)具有结构上的同源性。结果表明，pNP6-Sulfo-GlcNAc 1a具有较强的抑制病毒唾液酸酶活性(IC_(50)=2.8μM)。当1a的PNP基团被转化为对乙酰氨基苯基酮5(IC_&lt；50&gt；=30 mm)或被1-萘基6(IC_&lt；50&gt；=10μM)或正丙基酮8(IC_&lt；50&gt；=11μM)取代时，活性提高了近100倍。(5)用表面压力等温线和表面等离子激元研究了聚在朗缪尔单分子膜上的GM3和G3三糖之间的糖-糖相互作用。对GM3-GG3相互作用进行了SPR研究，以定量估计相互作用的亲和常数和特异性。Pn(Gg3)在GM3单分子膜上有较强的特异性吸附，其表观亲和常数K_a=2.5×10~(-6)M~(-1)~(-1)。我们发现，GM3中N-乙酰神经氨酸和GG3中GalNAc的NHAC基团在GM3-GG3相互作用中起着重要作用，PN(GG3)不仅识别GM3的某些特定部分，而且还识别整体上的三糖。较少

(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