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中文摘要
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项目摘要 细菌非磺酸和多糖的化学酶法合成 唾液酸是一类分布广泛的非磺酸(具有九个碳主链的α-酮酸)。 脊椎动物和一些致病菌。细菌还会产生尚未被分解的非磺酸 存在于动物体内。这些细菌特有的非磺酸已被细菌用作其 荚膜多糖(CPSS)和脂多糖(LPS)是细菌的毒力因子和 潜在的疫苗候选者。结构上定义的细菌CPSS、LPS和相应的 寡糖重复单元是研究其在细菌感染和微生物宿主中作用的重要探针 相互作用,包括它们对宿主免疫系统的影响。这些碳水化合物是诱人的合成 目标,但构成了重大的合成挑战。除了细菌特有的非磺酸外,它们还可以 含有其他在哺乳动物中未发现的单糖成分。糖苷键 细菌中发现的多糖也比哺乳动物多糖中的多糖更加多样。我们建议 建立高效的化学酶法合成细菌非磺酸及其多糖 病原菌的部分CPS和内毒素低聚糖。它们代表着重要的生物学意义和 具有综合挑战性的目标。在目前的提案期限内,重点将放在细菌多糖上 含有军团氨基酸及其衍生物。三个具体目标是:1、合成接受者和 一锅多酶(OPME)糖基化系统的单糖化学酶合子;2, 确定和表征候选的糖-1-P激酶、UDP-糖合成酶和糖基转移酶; 3、含军团氨基酸或细菌多糖重复单元的化学酶法合成 衍生品。确定的酶和设计的单糖是用于 获得不限于靶标的具有挑战性的合成碳水化合物和糖偶联物 建议书中所描述的。产生的低聚糖是更好地理解 细菌多糖的重要作用。它们也是合成结构定义的化合物的候选者 碳水化合物-蛋白质结合疫苗用于对抗细菌感染。
英文摘要
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.
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High-throughput closed-loop direct aberration sensing and correction for multiphoton imaging in live animals
  • 批准号:
    10572572
  • 项目类别:
  • 资助金额:
    $10.41万
  • 财政年份:
    2023
  • 负责人:
    Xi Chen
  • 依托单位:
Crosstalk between the ER Stress Response and Mitochondrial Fatty Acid Oxidation in MYC-driven Breast Cancer
  • 批准号:
    10581179
  • 项目类别:
  • 资助金额:
    $35.87万
  • 财政年份:
    2023
  • 负责人:
    Xi Chen
  • 依托单位:
Proteostasis Reprogramming in Mutant KRAS-Driven Cancers
  • 批准号:
    10587281
  • 项目类别:
  • 资助金额:
    $51.54万
  • 财政年份:
    2022
  • 负责人:
    Xi Chen
  • 依托单位:
A Life Course Approach to Understanding Racial and Ethnic Disparities in Alzheimer's Disease and Related Dementias and Health Care
  • 批准号:
    10650381
  • 项目类别:
  • 资助金额:
    $72.78万
  • 财政年份:
    2022
  • 负责人:
    Xi Chen
  • 依托单位:
海外基金