New strategies for expeditious oligosaccharide synthesis

快速合成寡糖的新策略

基本信息

批准号：
8180669
负责人：
ALEXEI V DEMCHENKO
金额：
$ 29.52万
依托单位：
UNIVERSITY OF MISSOURI-ST. LOUIS
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-01 至 2014-08-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8180669
关键词：
Address Advanced Development Ally Alzheimer&apos s Disease Amino Sugars Area Bacterial Infections Belief Biochemical Biological Biological Phenomena Biology Breathing Carbohydrate Chemistry Carbohydrates Cause of Death Chemicals Chemistry Complement Complex Development Diagnosis Diagnostic Discipline Disease Educational Curriculum Glycoconjugates Glycosides Goals Health Human Knowledge Laboratories Lead Learning Left Letters Life Light Malignant Neoplasms Medical Medicine Methodology Methods Molecular Conformation Nature Oligosaccharides Pathogenesis Pneumococcal Infections Prevention Process Property Protocols documentation Qualifying Research Research Personnel Research Training Science Scientist Septicemia Structure Students Surface Techniques Technology Therapeutic Training Programs Uncertainty Work analog arm base design glycosylation innovation insight novel programs research study tool

项目摘要

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.

描述（由申请人提供）：快速低聚糖合成的新策略复杂碳水化合物的功能与多种生物现象相关，特别是它们在危及生命的过程中的参与，已经为此类天然化合物提供了巨大的科学、诊断和应用价值。治疗潜力。为此，PI 实验室将工作重点放在与全球十大死因疾病（即癌症、肺炎球菌疾病、败血症和阿尔茨海默病）相关的碳水化合物上。这项工作的核心是相信，如果能够全面了解这些碳水化合物的结构、构象和特性，就可以促进疾病发病机制的阐明。因此，这可能会导致开发预防、诊断和治疗这些疾病的有效工具。本文提议扩展 PI 实验室发起的研究，以开发合成复杂碳水化合物的新技术。该提案的核心是开发正交寡糖合成的新策略。这些研究的基本原理是，一旦建立了通用方法，就应该可以使用这些方案来设计各种生物学上重要的或治疗上相关的化合物的合成。绝大多数天然复合碳水化合物含有通过O-糖苷键连接成低聚糖结构、寡糖的单体单元。因此，本文提出的研究也有望对所有研究生物有机物质的科学家具有广泛的方法学和实用价值。完成拟议的研究计划后，我们期望建立快速寡糖组装的新概念，并开发出适用的可靠工具包。合成各种复杂的糖结构。 PI 的主要承诺是在合成碳水化合物化学和相关学科领域维持一个充满活力的优秀研究项目，使学生成为富有创造力、富有成效的研究人员，能够在化学、生物学和医学之间建立重要的桥梁。 PI 相信，令人兴奋的科学发现将简化复杂寡糖和复合糖的合成，并有助于将新颖的见解作为学习工具纳入课程中。公共卫生相关性：拟议的研究计划对人类健康有双重影响。首先，本文概述的新合成策略将允许简化与许多致命疾病（包括癌症和细菌感染）相关的复杂碳水化合物的合成。毫无疑问，这些分子用于生物学研究可以显着促进基于碳水化合物的治疗和诊断剂的开发。另一个长期影响是，本科生和研究生研究人员将在该项目过程中接触到有价值的研究，预计这将使他们做好准备，在 21 世纪创新和推进各种与健康相关的学科。

项目成果

期刊论文数量（30）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Unexpected orthogonality of S-benzoxazolyl and S-thiazolinyl glycosides: application to expeditious oligosaccharide assembly.

S-苯并恶唑基和S-噻唑啉基糖苷的意外正交性：在快速寡糖组装中的应用。

DOI：
10.1021/ol802740b
发表时间：
2009-02-19
期刊：
Organic letters
影响因子：
5.2
作者：
Kaeothip, Sophon;Pornsuriyasak, Papapida;Rath, Nigam P.;Demchenko, Alexei V.
通讯作者：
Demchenko, Alexei V.

On orthogonal and selective activation of glycosyl thioimidates and thioglycosides: application to oligosaccharide assembly.

糖基硫代亚氨酸酯和硫代糖苷的正交和选择性激活：在寡糖组装中的应用。