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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.

复杂碳水化合物的功能与多种生物现象有关，特别是它们参与危及生命的过程，这类天然化合物具有巨大的科学、诊断和治疗潜力。为此，PI的实验室将精力集中在与全球十大死亡原因（即癌症、肺炎球菌病、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，如果对这些碳水化合物的结构、构象和性质有了全面的了解，就可以促进对疾病发病机制的阐明。因此，这可能导致开发预防、诊断和治疗这些疾病的有效工具。本文建议扩大PI实验室的研究，以开发合成复杂碳水化合物的新技术。本提案的核心是发展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，就有可能使用这些方案来设计各种生物重要或治疗相关化合物的合成。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的单体，即低聚糖。因此，本文提出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和实用价值。在完成拟议的研究计划后，我们希望建立快速低聚糖组装的新概念，并开发出适用于合成广泛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一个充满活力的有价值的研究项目，这将使学生成为有创造力、有生产力的研究人员，能够在化学、生物学和医学之间架起重要的桥梁。PI一直相信，令人兴奋的科学发现将简化复杂寡糖和糖缀合物的合成，并有助于将新的见解作为学习工具纳入课程。

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）

Expeditious oligosaccharide synthesis via selective, semi-orthogonal, and orthogonal activation.

DOI：
10.1016/j.carres.2011.05.004
发表时间：
2011-09-06
期刊：
CARBOHYDRATE RESEARCH
影响因子：
3.1
作者：
Kaeothip, Sophon;Demchenko, Alexei V.
通讯作者：
Demchenko, Alexei V.

Superarming of glycosyl donors by combined neighboring and conformational effects.

DOI：
10.1021/ol402371b
发表时间：
2013-09-20
期刊：
ORGANIC LETTERS
影响因子：
5.2
作者：
Heuckendorff, Mads;Premathilake, Hemali D.;Pornsuriyasak, Papapida;Madsen, Anders O.;Pedersen, Christian M.;Bols, Mikael;Demchenko, Alexei V.
通讯作者：
Demchenko, Alexei V.

2-Acylamido analogues of N-acetylglucosamine prime formation of chitin oligosaccharides by yeast chitin synthase 2.

酵母壳蛋白合酶2的N-乙酰葡萄糖素寡糖的N-乙酰葡萄糖素形成的2-酰胺类似物2。