Collaborative Research: Design of Templated Ceramic Materials for Separation and Purification of Complex Carbohydrates

合作研究：用于复杂碳水化合物分离和纯化的模板陶瓷材料的设计

• 批准号: 0967381
• 负责人: Stephen Rankin
• 金额: $ 30.11万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-15 至 2014-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0967381&HistoricalAwards=false
• 关键词: Collaborative; Research; Design; Templated; Ceramic

Complex carbohydrates play many integral roles in biological systems. Biologically active polysaccharides (glycans) interact with proteins on the outside of cells, and are involved in controlling communication, adhesion, and transport of material between cells. The need to isolate and purify specific carbohydrates for use as drugs has emerged from the realization that carbohydrates are central to many cell functions and disease states, ranging from cold sores to cancer. However, the technology to synthesize and purify specific carbohydrates is falling behind the ability of glycobiologists to identify the structure and function of carbohydrates. This project will develop microphase directed molecular imprinting (MDMI) of sol-gel ceramic materials to design selective, stable materials for the separation and purification of complex carbohydrates based on recognition of the glycan building blocks of glucose, glucosamine, and glucuronic acid. In MDMI, imprinting sites are anchored on the surface of self assembled surfactant micelles, and sol-gel polymerization of metal oxide precursors and organically modified silanes create a material complementary to the imprinting sites. The micelles reduce the need for solvents during processing, stabilize the material during drying, and serve as well-defined pore templates that can be removed after curing to make the imprinted sites accessible. A well designed MDMI process is hypothesized to produce materials that selectively adsorb the complex carbohydrate for which the imprinting sites were designed. This collaborative project employs the expertise of chemical and materials engineering and synthetic chemistry to focus synergistically on three critical aspects of the development of the MDMI process for molecules with acidic (glucuronic acid) and basic (glucosamine) functionality. The first aim addresses control of the interactions between material precursors and imprinting molecule to create a perfect binding pocket. The second aim addresses the design and predictive synthesis of a high porosity, accessible matrix to support the imprinted sites based on knowledge of surfactant phase behavior and interactions. The third aim addresses the synthesis of the imprinting molecules themselves specifically, molecules that effectively play dual roles as pore templates and molecular imprinting sites. Each one of these aims begins from easily accessible experimental systems and builds in complexity as milestones are reached toward the ultimate goal of imprinting complex polysaccharides. The molecular imprinting of ceramics through dual-use pore templating/molecular imprinting molecules is potentially transformative to the development of high performance adsorbents for the separation of functional polysaccharides. By combining the synthetic versatility of sol-gel materials and the selectivity of molecular imprinting, the proposed work will establish approaches to customizing ceramics through the knowledge of imprinting and carbohydrate binding mechanisms. Mimicry of the highly selective lock and key interaction between glycans and proteins within synthetic sol-gel matrices will be developed for the isolation of biologically relevant polysaccharides. Success of this project will enhance our knowledge of the role of carbohydrates in biological function, expand the commercial potential of these molecules, and develop personnel capable of leading the field of complex carbohydrate separations. The successful development of MDMI for saccharide-imprinted materials will advance synthetic saccharide purification, and also the recovery of valuable agricultural products and plant based drug discovery, and eventually provide for improved platforms for carbohydrate sensors and enzyme mimicking catalysts. The proposed project will highlight the critical role of bioseparations and develop outreach materials, research experiences, and curriculum that expand the impact of a new undergraduate Biopharmaceutical Engineering Certificate program at the University of Kentucky to graduate level education.

复杂的碳水化合物在生物系统中起许多不可或缺的作用。生物活性多糖（Glycans）与细胞外部的蛋白质相互作用，并参与细胞之间材料的通信，粘附和运输。从碳水化合物到许多细胞功能和疾病状态的核心，从唇疱疹到癌症，碳水化合物是许多细胞功能和疾病状态的核心。但是，合成和净化特定碳水化合物的技术落后于糖生物学家鉴定碳水化合物的结构和功能的能力。该项目将基于识别葡萄糖，葡萄糖胺和葡萄糖酸的聚糖构建块的识别，开发出溶胶 - 凝胶陶瓷材料的微小分子印迹（MDMI），以设计选择性的稳定材料，以分离和纯化复杂的碳水化合物。在MDMI中，烙印位点锚定在自组装表面活性剂胶束的表面上，并将金属氧化物前体的溶胶 - 凝胶聚合和有机修饰的硅烷固定在印记地点互补。胶束在加工过程中减少了对溶剂的需求，在干燥过程中稳定材料，并提供定义明确的孔模板，这些模板可以在固化后可以去除，以使刻痕的地点可访问。假设设计良好的MDMI工艺可以产生有选择地吸附的材料，这些材料吸附了设计印迹位点的复杂碳水化合物。该协作项目采用化学和材料工程和合成化学的专业知识，以协同关注具有酸性（葡萄糖酸）和碱性（葡萄糖胺）功能的MDMI过程开发的三个关键方面。第一个目的解决了对材料前体和印记分子之间相互作用的控制，以创建一个完美的绑定袋。第二个目的是根据表面活性剂相行为和相互作用的知识来支持高孔隙率，可访问矩阵的设计和预测合成。第三个目的是针对烙印分子本身的综合，这些分子有效地作为孔模板和分子烙印位点起着双重作用。这些目标中的每一个都始于易于访问的实验系统，并随着里程碑的实现，以构成印记复杂多糖的最终目标。陶瓷通过双重用途的孔隙/分子印迹分子的分子印记可能会转化为高性能吸附剂的发展，以分离功能性多糖。通过结合溶胶 - 凝胶材料的合成多功能性和分子烙印的选择性，提出的工作将通过了解印迹和碳水化合物结合机制来建立定制陶瓷的方法。将开发合成溶胶 - 凝胶矩阵中聚糖和蛋白质之间高度选择性锁定的模仿和关键相互作用，以分离生物相关的多糖。该项目的成功将增强我们对碳水化合物在生物功能中的作用，扩大这些分子的商业潜力的知识，并发展能够领导复杂碳水化合物分离领域的人员。 MDMI成功开发用于糖水含量的材料将推进合成糖的纯化，还可以回收有价值的农产品和植物性药物发现，并最终为改进的碳水化合物传感器和模仿催化剂的酶提供了改进的平台。拟议的项目将突出生物序列的关键作用，并开发外展材料，研究经验和课程，从而扩大肯塔基大学新的本科生物制药工程证书计划的影响到研究生水平的教育。