寡糖类抗癌疫苗衍生物的酶法合成

项目名称： 寡糖类抗癌疫苗衍生物的酶法合成

项目编号： No.20802037

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 医药、卫生

项目作者： 赵炜

作者单位： 南开大学

项目金额： 18万元

中文摘要： 细胞表面糖抗原的表达通常在细胞癌化过程中有较大改变，而且某些特定的寡糖只在某些特定的癌细胞上表达，因此特殊结构的寡糖可以作为抗肿瘤疫苗。目前，该领域存在两大技术瓶颈。首先，寡糖抗原很难从癌细胞中大量提取，化学和酶法合成是解决这一问题的主要途径。其次，这些单个寡糖的抗原性很低。为了提高寡糖的抗原性，激发人体产生有效的免疫反应，有效的途径之一是对寡糖的结构进行衍生化。本课题拟以寡糖Lewis-y为目标和母体分子，以酶法合成为手段，通过糖基衍生化来解决上述两个瓶颈。我们的技术平台包括：1）新的烯糖方法学和稀有糖糖库的建立。2）扩展工具酶的底物多样性，并以此为基础合成寡糖衍生物。本项目的实施将极大丰富酶法合成寡糖及其衍生物的技术手段，并对抗肿瘤疫苗的研究和临床应用有着重大推动作用。

中文关键词： 寡糖；肿瘤；疫苗；酶法；衍生物

英文摘要： Altered glycosylation patterns are often a hallmark of the tumour phenotype. Each type of malignant tissue is characterized by a distinct set of changes in glycan expression. Therefore, these glycans can be used for preparation of anti-tumour vaccines. There are two technical bottleneck in this field. Firstly, the difficulty to extract abundant antigens from cancer cell. In order to solve this problem, the potent approach is chemical and enzymatic synthesis of tumour associated glycans. Secondly, the low immunogenicity of these glycans. In order to augment the immunogenicity of glycan-based vaccines, the effective approache is the chemical modification of monosaccharide structures. In our proposal, we choose Lewis-y as target and template molecule, using chem-enzymatic synthesis approachs. The mentioned bottlenecks would be overcomed by derivation of the template molecule. Our technical platform includes as follow: 1) new methodology of preparing glycols and establishing the carbohydrate library of uncommon sugars. 2) expanding enzymatic substrate diversity and synthesizing the derivatives of oligosaccharide antigens. The implement of our project will greatly enrich enzymatic synthesis of oligosaccharides and the derivatives, which contributes greatly to impel the study of anti-tumour vaccines and their clinical applications.

英文关键词： Oligosaccharide; tumor; vaccine; enzymatic; derivative