Development and Application of Surface-Tethered Iterative Carbohydrate Synthesis

表面束缚碳水化合物迭代合成的开发与应用

• 批准号: 7939800
• 负责人: Keith J. Stine
• 金额: $ 26.16万
• 依托单位: UNIVERSITY OF MISSOURI-ST. LOUIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7939800
• 关键词: Address; Alzheimer' s Disease; Area; Arts; Attention; Autoimmune Diseases; Belief; Biochemical; Biological; Biological Assay; Biological Phenomena; Biological Sciences; Carbohydrate Chemistry; Carbohydrates; Cause of Death; Chemicals; Chemistry; Collaborations; Communication; Communities; Complex; Development; Diagnosis; Diagnostic; Disease; Drug Delivery Systems; Generations; Genomics; Glycobiology; Glycoconjugates; Glycolipids; Goals; Gold; Grant; Health; Health Sciences; Human; Knowledge; Laboratories; Lead; Learning; Libraries; Link; Malignant Neoplasms; Manuscripts; Medical; Methodology; Methods; Molecular Conformation; Nanotechnology; National Institute of General Medical Sciences; Nature; Oligosaccharides; Organic Synthesis; Participant; Pathogenesis; Pneumococcal Infections; Polysaccharides; Postdoctoral Fellow; Preparation; Prevention; Process; Property; Proteomics; Reaction; Reporting; Research; Research Personnel; Screening procedure; Septicemia; Solid; Sorting - Cell Movement; Stem cells; Structure; Students; Surface; Testing; Therapeutic; Therapeutic Agents; Training; Trust; Work; base; carbohydrate binding protein; combinatorial; design; experience; flexibility; glycosylation; high throughput screening; high throughput technology; improved; innovation; interdisciplinary collaboration; meetings; method development; monolayer; multidisciplinary; nanomaterials; new technology; novel; novel strategies; programs; public health relevance; self assembly; skills; stem cell biology; success; sugar; tool

DESCRIPTION (provided by applicant): Complex carbohydrates are involved in a broad variety of biological phenomena and their involvement in disease processes, in particular, have given this class of natural compounds a tremendous diagnostic and therapeutic potential. To this end, the PI's and co-PI's laboratories have focused their research efforts towards carbohydrates associated with diseases that rank among the top 10 leading causes of death worldwide, i.e. cancer, pneumococcal disease, septicemia, and Alzheimer's disease. At the core of this effort is the belief that if a comprehensive knowledge of the structure, conformation, and properties of these carbohydrates were available, elucidation of the mechanisms for the pathogenesis of these diseases could be facilitated. Consequently, this could lead to the development of effective tools for the prevention, diagnosis, and/or treatment of these diseases. The long-term goals of the PI's and co-PI's research programs are to make complex carbohydrates more accessible to general chemical, biochemical, medical and industrial audiences, and thereby keep pace with the exploding areas of glycobiology and related health sciences. Proposed herein is the expansion of studies initiated in our laboratories for the development of novel high-throughput technologies for oligosaccharide and glycoconjugate synthesis. At the core of this proposal is the development of a new strategy for supported synthesis called STICS (Surface-Tethered Iterative Carbohydrate Synthesis). The intellectual merit of the proposed research lies in its significant contributions to the field of basic and applied synthetic carbohydrate, surface, and nanomaterial chemistries upon its successful completion. Precisely, the success of this endeavor will not only advance the field of chemistries mentioned, but also fundamentally contribute to further development of glyco- and nanotechnology in general. We trust that the proposed developments will lead to the discovery of novel methodologies for the efficient synthesis and high throughput screening of carbohydrate-based libraries and therapeutics. A broader and long-term impact of this work relate to the professional training in surface, preparative organic, carbohydrate, bioorganic, and materials chemistry that undergraduate, graduate and post-doctoral research participants will receive. In addition, the multidisciplinary nature of the proposed research will allow students to expand their scientific base in an intellectual and practical sense. During their laboratory experience they will learn important tools that allow obtain, modify, and analyze organic molecules and nanomaterials by means of developing new methodologies and participating in the elaboration of state-of-the-art, multi-step syntheses. Student researchers will also become integrated into the scientific community through the preparation of manuscripts and attendance at professional meetings. As a consequence, students will develop better communication skills while also being exposed to scientific discourse. Finally, the proposed research will ultimately strengthen interdisciplinary collaborations with biomedical researchers. PUBLIC HEALTH RELEVANCE: The proposed research will benefit human health by developing a new strategy for synthesizing carbohydrates significant in diagnosing and treating diseases including cancer and autoimmune diseases, and in the development of new therapies based on stem cells. The new technology for surface supported carbohydrate synthesis will result in these molecules becoming more accessible for biological studies that can lead to development of therapeutic agents. The nanomaterials used for our new approach to supported syntheses can also be used for diagnostic assays and stem cell biology sorting applications using the carbohydrates made as a part of this project.

描述（由申请人提供）：复合碳水化合物参与多种生物现象，特别是它们参与疾病过程，使这类天然化合物具有巨大的诊断和治疗潜力。为此，PI和co-PI的实验室将其研究工作集中在与全球十大主要死亡原因之一的疾病相关的碳水化合物上，即癌症、肺炎球菌病、败血症和阿尔茨海默病。这项工作的核心是相信，如果这些碳水化合物的结构，构象和性质的全面知识是可用的，阐明这些疾病的发病机制可以促进。因此，这可能导致开发用于预防、诊断和/或治疗这些疾病的有效工具。PI和co-PI的研究计划的长期目标是使复杂的碳水化合物更容易为一般化学，生物化学，医学和工业观众所接受，从而跟上糖生物学和相关健康科学的爆炸性领域。本文提出的是扩展我们实验室启动的研究，以开发用于寡糖和糖缀合物合成的新型高通量技术。该提案的核心是开发一种新的支持合成策略，称为STICS（表面束缚迭代碳水化合物合成）。拟议研究的智力价值在于其成功完成后对基础和应用合成碳水化合物，表面和纳米材料化学领域的重大贡献。准确地说，这一奋进的成功不仅将推动上述化学领域的发展，而且将从根本上促进糖和纳米技术的进一步发展。我们相信，所提出的发展将导致发现新的方法的有效合成和高通量筛选碳水化合物为基础的图书馆和治疗。这项工作的更广泛和长期的影响涉及表面，制备有机，碳水化合物，生物有机和材料化学的专业培训，本科生，研究生和博士后研究参与者将获得。此外，拟议研究的多学科性质将使学生能够在智力和实践意义上扩大他们的科学基础。在他们的实验室经验，他们将学习重要的工具，允许获得，修改和分析有机分子和纳米材料通过开发新的方法和参与国家的最先进的，多步合成的阐述。学生研究人员还将通过编写手稿和参加专业会议融入科学界。因此，学生将发展更好的沟通技巧，同时也接触到科学话语。最后，拟议的研究将最终加强与生物医学研究人员的跨学科合作。 公共卫生关系：拟议的研究将通过开发一种新的策略来合成碳水化合物，这对诊断和治疗包括癌症和自身免疫性疾病在内的疾病以及开发基于干细胞的新疗法具有重要意义，从而有益于人类健康。表面支持碳水化合物合成的新技术将使这些分子更容易用于生物学研究，从而导致治疗剂的开发。用于我们支持合成的新方法的纳米材料也可以用于诊断分析和干细胞生物学分选应用，使用作为该项目一部分的碳水化合物。