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Heparin Glycan Microarray for Screening

用于筛选的肝素聚糖微阵列

基本信息

批准号：
7421026
负责人：
ROBERT J LINHARDT
金额：
$ 20万
依托单位：
SOLIDUS BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-15 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7421026
关键词：
Anabolism Anticoagulants Antithrombin III Area Binding Biological Biology Biopolymers Cell Communication Cells Chemistry Clinical Collection Communication Complex Confidential Information Cytochrome P450 Development Diagnostic Discipline Drug Evaluation Drug Interactions Drug toxicity Enzymes Escherichia coli Genomics Glycosaminoglycans Goals Golgi Apparatus Heparin Heparitin Sulfate Human Laboratories Lead Liquid substance Modification NIH Program Announcements Numbers Oligosaccharides Organ Patients Pharmaceutical Preparations Pharmacologic Substance Phase Polysaccharides Process Proteomics Recombinants Research Sampling Science Screening procedure Small Business Technology Transfer Research Specificity Speed Structure Structure-Activity Relationship Technology Tissues Toxic effect Treatment Protocols Uridine Diphosphate Sugars Writing base capsular polysaccharide K5 cationic antimicrobial protein CAP 37 commercial application design drug development glycosyltransferase high throughput analysis human RPL29 protein metabolomics new technology next generation programs response small molecule

项目摘要

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.

描述（由申请人提供）：拟议的研究计划将 Solidus 技术应用于微阵列、生物催化和筛选，并将 Linhardt 小组在肝素/硫酸乙酰肝素方面的专业知识应用于糖组学领域。糖组学是对聚糖结构与功能关系的综合研究，是代谢组学的一个子学科，是基因组学和蛋白质组学的下一步。肝素糖胺聚糖（肝素和硫酸乙酰肝素）是结构最复杂的生物聚合物之一。这些聚糖携带并存储在涉及细胞间相互作用和通讯的几乎所有病理和病理生理过程中至关重要的重要生物信息。第一阶段 STTR 提案的具体目标和里程碑是： 1. 制备肝素聚糖微阵列； 2. 用高度特异性的肝素结合蛋白抗凝血酶 III 探测该微阵列； 3.制备酶修饰的heparosan微阵列； 4. 用一组肝素结合蛋白探测该微阵列以检查结合特异性； 5.基于糖基转移酶延伸和肝素寡糖受体的酶促修饰制备结构明确的聚糖微阵列，用于用肝素结合蛋白进行探测。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、评估拮抗肝素/硫酸乙酰肝素与肝素结合蛋白相互作用的小分子药物以及诊断应用中生物样品的快速筛选。将准备第二阶段提案来开发这些商业应用。