New strategies for expeditious oligosaccharide synthesis

描述(由申请人提供)：快速合成寡糖的新策略复杂碳水化合物与各种生物现象有关的功能及其在威胁生命的过程中的参与，特别是赋予了这类天然化合物巨大的科学、诊断和治疗潜力。为此，PI的实验室将重点放在与碳水化合物相关的疾病上，这些疾病是全球前十大死亡原因之一，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，如果对这些碳水化合物的结构、构象和性质有全面的了解，就可能有助于阐明疾病的发病机制。因此，这可能导致开发有效的工具来预防、诊断和治疗这些疾病。在此提出的是在PI的实验室中为开发合成复杂碳水化合物的新技术而启动的研究的扩展。这一提议的核心是开发正交低聚糖合成的新策略。这些研究的基本原理是，一旦建立了一般的方法学，就应该可以使用这些方案来设计各种具有生物重要性或治疗相关的化合物的合成。绝大多数天然复杂碳水化合物含有单体单元，通过O-糖苷键连接成低聚糖结构、寡糖。因此，本文建议的研究也有望对所有从事生物有机物质研究的科学家具有广泛的方法学和实用价值。在完成建议的研究计划后，我们期望建立新的低聚糖快速组装概念，并开发出适用于合成多种复杂糖结构的可靠工具包。PI的主要承诺是在合成碳水化合物化学和相关学科领域保持活跃的、有价值的研究计划，使学生准备成为创造性的、多产的研究人员，能够在化学、生物和医学之间建立必要的桥梁。PI一直相信，令人兴奋的科学发现将简化复杂低聚糖和糖共轭化合物的合成，并有助于将新的见解作为学习工具纳入课程。 公共卫生相关性：拟议的研究计划对人类健康的影响是双重的。首先，这里概述的新的合成策略将允许简化复杂碳水化合物的合成，这些碳水化合物与包括癌症和细菌感染在内的许多致命疾病有关。毫无疑问，这些分子可用于生物学研究，可以显著推动碳水化合物治疗和诊断试剂的发展。另一个长期影响是，本科生和研究生研究人员在这个项目过程中将不得不进行有价值的研究，预计这将使他们具备在21世纪创新和推进各种与健康相关的学科的能力。

DESCRIPTION (provided by applicant): New Strategies for Expeditious Oligosaccharide Synthesis Functions of complex carbohydrates related to a broad variety of biological phenomena and their involvement in life-threatening processes, in particular, have given this class of natural compounds a tremendous scientific, diagnostic and therapeutic potential. To this end, the PI's laboratory has focused its effort toward carbohydrates associated with diseases that rank among the top 10 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 pathogenesis of the disease could be facilitated. Consequently, this could lead to the development of effective tools for the prevention, diagnosis, and treatment of these diseases. Proposed herein is the expansion of studies initiated in the PI's laboratory for the development of novel techniques for the synthesis of complex carbohydrates. At the core of this proposal is the development of new strategies for orthogonal oligosaccharide synthesis. The rationale for these studies is that once a general methodology has been established, it should be possible to use these protocols to design the syntheses of various biologically important or therapeutically relevant compounds. A vast majority of natural complex carbohydrates contain monomeric units connected via O-glycosidic linkages into oligomeric glycostructures, oligosaccharides. Therefore, the studies proposed herein are also expected to be of broad methodological and practical value to all scientists working with bioorganic substances Upon completion of the proposed research program, we expect to have established novel concepts for rapid oligosaccharide assembly and to have developed reliable toolkits applicable to the synthesis of a broad range of complex glycostructures. The PI's major commitment is to maintain a vigorous meritorious research program in the area of synthetic carbohydrate chemistry and allied disciplines that will prepare students to be creative, productive researchers capable of building essential bridges among chemistry, biology and medicine. It has been the PI's belief that exciting scientific discoveries will simplify the synthesis of complex oligosaccharides and glycoconjugates and help to incorporate novel insights into the curriculum as learning tools. PUBLIC HEALTH RELEVANCE: The impact of the proposed research program to human health is two-fold. First, the novel synthetic strategies outlined herein will allow for streamlining the synthesis of complex carbohydrates associated with many fatal diseases including cancer and bacterial infections. Without a doubt, the availability of these molecules for biological studies could significantly advance the development of carbohydrate-based therapeutic and diagnostic agents. Another long-term impact is the exposure undergraduate and graduate researchers will have to meritorious research during the course of this project, which is expected to leave them well equipped to innovate and advance various health-related disciplines in the 21st century.