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Chemoenzymatic synthesis of bacterial polysaccharides

细菌多糖的化学酶法合成

基本信息

批准号：
9981827
负责人：
Laura L Kiessling
金额：
$ 72.04万
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：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9981827
关键词：
ATP-Binding Cassette Transporters Address Adhesions Anabolism Bacteria Bacterial Polysaccharides Biological Biomedical Research Cell surface Chondroitin Communicable Diseases Complex Development Diagnosis Diagnostic Diphosphates Enzymes Galactans Generations Genus Mycobacterium Glycobiology High Pressure Liquid Chromatography Human Immune system Immunomodulators In Vitro Individual Laboratories Length Lipids Mediating Mediator of activation protein Monosaccharides Oligosaccharides Paper Pathogenicity Pathway interactions Polymerase Polysaccharides Preparation Production Protocols documentation Publications Reaction Reagent Research Research Personnel Structure System Technology Vaccine Design Vaccines Validation Variant Virulence Factors base carbohydrate binding protein chemical synthesis experience lipooligosaccharide medical specialties microbial polymerization programs reconstitution research and development web site

项目摘要

Chemoenzymatic synthesis of bacterial polysaccharides Project Summary The bacterial cell surface is decorated with remarkable variations of polysaccharide structures including capsular polysaccharides (CPS), O-polysaccharides (O-PS), and exopolysaccharides (EPS). These polysaccharides mediate interactions between the bacterium and its host. Many are important virulence factors, adhesion mediators, or immunomodulators. Because their composition differs dramatically from that of host glycans, multiple bacterial polysaccharides have been used to develop vaccines to protect human from a diverse array of bacterial infectious diseases. To date, these polysaccharides have been commonly isolated from the bacterial cultures and therefore consist of heterogeneous mixtures. Structurally defined polysaccharides with defined numbers of repeating units are not readily available. With the combined expertise of three groups on efficient one-pot multienzyme chemoenzymatic synthesis of oligosaccharide repeating units, polymerization of lipooligosaccharide repeating units for the formation of Wzy-dependent bacterial polysaccharides and polysaccharide synthase-catalyzed production of bacterial polysaccharides, structurally defined polysaccharides with designated numbers of oligosaccharide repeating units will be synthesized. These compounds are valuable probes for glycan microarray studies and candidates for the development of diagnostics, immunomodulators, and vaccines. Optimal storage and reaction conditions will be identified. Enzymes and reagents will be assembled in convenient-to-store and easy-to-use kits. Protocols for synthesis and purification will be established and shared by publication of papers and on a designated website. These kits will allow non-specialists to carry out the synthesis.

细菌多糖的化学酶合成