权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Chemoenzymatic synthesis of bacterial nonulosonic acids and glycans

细菌非酮糖酸和聚糖的化学酶法合成

基本信息

批准号：
10364735
负责人：
Xi Chen
金额：
$ 30.78万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-05 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10364735
关键词：
Acids Acinetobacter baumannii Anabolism Animals Antibiotics Antibodies Bacteria Bacterial Infections Bacterial Polysaccharides Carbohydrates Carbon Chemicals Complex Conjugate Vaccines Development Enterobacter cloacae Enzyme Activation Enzymes Escherichia coli Excision Family Funding Future Generations Glycoconjugates Glycosides Immune system In Situ Keto Acids Libraries Ligase Lipopolysaccharides Mammals Methods Monitor Monosaccharides Oligosaccharides Phosphotransferases Polysaccharides Process Production Propylamines Proteins Reaction Reagent Research Role Sialic Acids Surface System Uridine Diphosphate Galactose Uridine Diphosphate Sugars Vertebral column Vertebrates Virulence Factors chemical synthesis combat design glycosylation glycosyltransferase host-microbe interactions improved inhibitor pathogenic bacteria sugar sugar nucleotide tool vaccine candidate

项目摘要

Project Summary Chemoenzymatic synthesis of bacterial nonulosonic acids and glycans Sialic acids are a family of wide-spread nonulosonic acids (alpha-keto acids with a nine-carbon backbone) in vertebrates and in some pathogenic bacteria. Bacteria also produce nonulosonic acids that have not been found in animals. These bacterium-specific nonulosonic acids have been used by bacteria as part of their capsular polysaccharides (CPSs) and lipopolysaccharides (LPSs) which are bacterial virulence factors and potential vaccine candidates. Structurally defined bacterial CPSs, LPSs, and the corresponding oligosaccharide repeating units are important probes to study their roles in bacterial infection and microbe-host interaction including their influence on host immune systems. These carbohydrates are attractive synthetic targets but pose significant synthetic challenges. In addition to bacterial specific nonulosonic acids, they may contain other monosaccharide building blocks that have not been found in mammals. The glycosidic linkages found in bacterial polysaccharides are also much more diverse than those in mammalian glycans. We propose to develop efficient chemoenzymatic methods to synthesize bacterial nonulosonic acids and their glycans as part of CPS and LPS oligosaccharides of pathogenic bacteria. These represent biologically important and synthetically challenging targets. In the current proposal duration, the focus will be on bacterial glycans containing legionaminic acid and their derivatives. Three specific aims are: 1, Synthesize acceptors and monosaccharide chemoenzymatic synthons for one-pot multienzyme (OPME) glycosylation systems; 2, Identify and characterize candidate sugar-1-P kinases, UDP-sugar synthetases, and glycosyltransferases; and 3, Chemoenzymatic synthesis of bacterial polysaccharide repeating units containing legionaminic acid or derivatives. The enzymes identified and the monosaccharides designed are important tools and reagents for accessing synthetic challenging carbohydrates and glycoconjugates that are not limited to the targets described in the proposal. The oligosaccharides produced are essential probes for better understanding the important roles of bacterial polysaccharides. They are also candidates for synthesizing structurally defined carbohydrate-protein conjugate vaccines to combat bacterial infections.

项目总结