首页> 外文学位 >Part I. Synthesis of lipid A derivatives and their interactions with lipid A binding agents. Part II. Synthesis of glycosphingolipids to study natural killer T cell stimulation.
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Part I. Synthesis of lipid A derivatives and their interactions with lipid A binding agents. Part II. Synthesis of glycosphingolipids to study natural killer T cell stimulation.

机译:第一部分:脂质A衍生物的合成及其与脂质A结合剂的相互作用。第二部分合成鞘糖脂以研究自然杀伤性T细胞刺激。

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摘要

Part I. Lipid A is the causative agent of Gram-negative sepsis, a leading cause of mortality among hospitalized patients. Compounds that bind lipid A can limit its detrimental effects. To better understand interactions of lipid A and lipid A binding agents, lipid A derivatives were prepared with incrementally varied lipid chain lengths. These lipid A derivatives were used to study their interactions with polymyxins and cationic steroid antibiotics using isothermal titration calorimetry and fluorescence spectroscopy, respectively. To develop cationic steroid antibiotics with high affinities for lipid A, combinatorial methods were used and fluorophore appended lipid A derivatives were prepared as probes for "on-bead" screening.; Part II. Natural killer T cells (NKT cells) are a subpopulation of T cells that control multiple immune responses including autoimmunity, antitumor, and allergic activities. In response to stimulation caused by glycolipids presented by CD1d, NKT cells are capable of rapidly producing a variety of cytokines to exert significant controls on the broader T-cell pool. To search for the natural ligand(s) of CD1d presentation and NKT cell stimulation, three sequences of glycosphingolipids were prepared as candidates: (1) 3″-O-sulfo-glycosylceramides; (2) globosides and isoglobosides; (3) alpha-uronosylceramides from LPS-negative Gram-negative bacteria Sphingomonas capsulata. Among these glycosylceramides, iGb3 was identified as an endogenous antigen of CD1d restricted NKT cells. Our findings also suggested that bacteria Sphingomonas capsulata were directly detected by NKT cells through specific recognition of alpha-uronosylceramides in bacterial cell walls.
机译:第一部分:脂质A是革兰氏阴性败血症的病原体,是住院患者死亡的主要原因。结合脂质A的化合物可以限制其有害作用。为了更好地理解脂质A和脂质A结合剂的相互作用,制备了具有逐渐变化的脂质链长度的脂质A衍生物。这些脂质A衍生物分别通过等温滴定热法和荧光光谱法研究了它们与多粘菌素和阳离子类固醇抗生素的相互作用。为了开发对脂质A具有高亲和力的阳离子甾类抗生素,使用了组合方法,并准备了附有荧光团的脂质A衍生物作为“珠子”筛选的探针。第二部分天然杀伤性T细胞(NKT细胞)是控制多种免疫反应(包括自身免疫,抗肿瘤和过敏活性)的T细胞的一个亚群。响应由CD1d产生的糖脂引起的刺激,NKT细胞能够快速产生多种细胞因子,从而对更广泛的T细胞库进行重要控制。为了寻找CD1d呈递和NKT细胞刺激的天然配体,制备了三种糖鞘脂序列作为候选:(1)3″ -O-磺基-糖基神经酰胺; (2)糖苷和异糖苷; (3)来自LPS阴性革兰氏阴性细菌荚膜鞘氨醇单胞菌的α-尿苷神经酰胺。在这些糖基神经酰胺中,iGb3被鉴定为CD1d限制性NKT细胞的内源性抗原。我们的发现还表明,NKT细胞通过特异性识别细菌细胞壁中的α-尿苷神经酰胺直接检测到了荚膜鞘氨醇单胞菌。

著录项

  • 作者

    Yin, Ning.;

  • 作者单位

    Brigham Young University.;

  • 授予单位 Brigham Young University.;
  • 学科 Chemistry Organic.; Health Sciences Immunology.; Chemistry Biochemistry.; Health Sciences Pharmacology.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 222 p.
  • 总页数 222
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 有机化学;预防医学、卫生学;生物化学;药理学;
  • 关键词

  • 入库时间 2022-08-17 11:42:50

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