Heparin Glycan Microarray for Screening

描述（由申请人提供）：拟议的研究项目将Solidus技术应用于微阵列、生物催化和筛选，并将Linhardt集团在肝素/硫酸肝素方面的专业知识应用于糖组学领域。糖组学是对糖结构-功能关系的综合研究，是代谢组学的一个分支学科，是基因组学和蛋白质组学的下一步。肝素糖胺聚糖（肝素和硫酸肝素）是结构最复杂的生物聚合物之一。这些聚糖携带和储存重要的生物信息，在几乎所有涉及细胞相互作用和通讯的病理和病理生理过程中至关重要。第一阶段STTR提案的具体目标和里程碑是：制备肝素聚糖微阵列；2. 用高特异性肝素结合蛋白抗凝血酶III探测微阵列；3. 制备酶修饰肝磷脂微阵列；4. 用肝素结合蛋白的集合探测该微阵列以检测结合特异性；和5。基于糖基转移酶延伸和肝素寡糖受体的酶修饰，制备结构明确的聚糖微阵列，用于肝素结合蛋白的探测。第一阶段将重点开发开发HepGly芯片所需的核心技术，作为筛选与肝素结合蛋白相互作用的糖组学平台。HepGly微阵列的潜在应用包括开发下一代基于肝素的药物，评估与肝素结合蛋白相互作用的肝素/硫酸肝素拮抗的小分子药物以及诊断应用中生物样品的快速筛选。将编制第二阶段提案，以开发这些商业应用。

DESCRIPTION (provided by applicant): The proposed research program applies Solidus technology in microarraying, biocatalysis, and screening and the Linhardt group's expertise in heparin/heparan sulfate to the field of glycomics. Glycomics, the comprehensive study of glycan structure-function relationship, is a sub-discipline of metabolomics and the next step beyond genomics and proteomics. Heparin glycosaminoglycans (heparin and heparan sulfate) are among the most structural complex biopolymers. These glycans carry and store significant biological information crucial in virtually all pathological and pathophysiological processes involving cell-cell interaction and communication. The specific aims and milestones of this Phase I STTR proposal are to: 1. prepare a heparin glycan microarray; 2. probe this microarray with the highly specific heparin-binding protein, antithrombin III; 3. prepare an enzyme-modified heparosan microarray; 4. probe this microarray with a collection of heparin-binding proteins to examine binding specificity; and 5. prepare a structurally defined glycan microarray based on the glycosyltransferase extension, and enzymatic modification of heparosan oligosaccharide acceptors for probing with heparin-binding proteins. Phase I will focus on developing the core technology required for developing a HepGly chip as a glycomics platform for screening interactions with heparin-binding proteins. Potential applications for a HepGly microarray include the development of the next generation of heparin-based drugs, the evaluation small molecule drugs that antagonize with heparin/heparan sulfate interaction with heparin-binding proteins and the rapid screening of biological samples in diagnostic applications. A phase II proposal will be prepared to develop these commercial applications.