GLYCAN ARRAYS FOR HIGH THROUGHPUT SCREENING OF VIRUSES

    公开(公告)号:US20150160217A1

    公开(公告)日:2015-06-11

    申请号:US14376837

    申请日:2011-04-12

    IPC分类号: G01N33/569

    摘要: Glycan arrays that can detect and distinguish between various sub-types and strains of influenza virus are provided. Methods for using the glycan arrays with assays using nanoparticle amplification technique are disclosed. Sandwich assays using gold nanoparticles conjugated to phage particles comprising influenza virus-specific antibodies for detecting multiple serotypes using a single reaction are provided. Plurality of glycans directed to specific target HA of influenza virus comprises the array. Detector molecules comprising noble metals conjugated to (a) phage display particles expressing antibodies against hemagglutinin and (b) neuraminidase binding agents are disclosed.

    摘要翻译: 提供了可以检测和区分各种亚型和流感病毒株的糖阵列。 公开了使用纳米颗粒扩增技术的测定法使用聚糖阵列的方法。 提供使用与包含用于使用单个反应检测多种血清型的流感病毒特异性抗体的噬菌体颗粒缀合的金纳米颗粒的三明治测定。 针对流感病毒的特定目标HA的多种聚糖包括阵列。 公开了包含与(a)噬菌体缀合的贵金属的检测分子,其显示表达针对血凝素的抗体的颗粒和(b)神经氨酸酶结合剂。

    Compositions and methods for identifying response targets and treating flavivirus infection responses
    35.
    发明授权
    Compositions and methods for identifying response targets and treating flavivirus infection responses 有权
    用于鉴定反应目标和治疗黄病毒感染反应的组合物和方法

    公开(公告)号:US08460669B2

    公开(公告)日:2013-06-11

    申请号:US13106046

    申请日:2011-05-12

    IPC分类号: A61K39/395 A61K39/285

    摘要: Cellular receptors are identified that induce plasma leakage and other negative effects when infected with flaviviruses, such as dengue virus or Japanese encephamyelitis virus. Using fusion proteins disclosed herein, the receptors to which a pathogen, such as flavivirus, binds via glycan binding are determined. Once the receptors are determined, the effect of binding to a particular receptor may be determined, wherein targeting of the receptors causing a particular symptom may be targeted by agents that interrupt binding of the pathogen to the receptor. Accordingly, in the case of dengue virus and Japanese encephamyelitis virus, TNF-α is released when the pathogen binds to the DLVR1/CLEC5A receptor. Interrupting the DLVR1/CLEC5A receptor with monoclonal antibodies reduced TNF-α secretion without affecting secretion of cytokines responsible for viral clearance thereby increasing survival rates in infected mice from nil to around 50%.

    摘要翻译: 鉴定当感染黄病毒如登革热病毒或日本脑炎病毒时诱导血浆渗漏和其它负面影响的细胞受体。 使用本文公开的融合蛋白,确定病原体(例如黄病毒)通过聚糖结合结合的受体。 一旦确定了受体,就可以确定与特定受体结合的作用,其中导致特定症状的受体的靶向可能被阻断病原体与受体结合的试剂所靶向。 因此,在登革热病毒和日本脑炎病毒的情况下,当病原体与DLVR1 / CLEC5A受体结合时,TNF-α被释放。 用单克隆抗体中断DLVR1 / CLEC5A受体降低TNF-α分泌,而不影响负责病毒清除的细胞因子分泌,从而将感染小鼠的存活率从零增加到约50%。

    ALKYNYL SUGAR ANALOGS FOR LABELING AND VISUALIZATION OF GLYCOCONJUGATES IN CELLS
    37.
    发明申请
    ALKYNYL SUGAR ANALOGS FOR LABELING AND VISUALIZATION OF GLYCOCONJUGATES IN CELLS 审中-公开
    用于在细胞中标记和观察甘油三酯的ALKYNYL糖模拟物

    公开(公告)号:US20120149887A1

    公开(公告)日:2012-06-14

    申请号:US13159339

    申请日:2011-06-13

    IPC分类号: C07H15/04 C07H19/10

    摘要: Methods for metabolic oligosaccharide engineering that incorporates derivatized alkyne-bearing sugar analogs as “tags” into cellular glycoconjugates are disclosed. Alkynyl derivatized Fuc and alkynyl derivatized ManNAc sugars are incorporated into cellular glycoconjugates. Chemical probes comprising an azide group and a visual or fluorogenic probe and used to label alkyne-derivatized sugar-tagged glycoconjugates are disclosed. Chemical probes bind covalently to the alkynyl group by Cu(I)-catalyzed [3+2] azide-alkyne cycloaddition and are visualized at the cell surface, intracellularly, or in a cellular extract. The labeled glycoconjugate is capable of detection by flow cytometry, SDS-PAGE, Western blot, ELISA, confocal microscopy, and mass spectrometry.

    摘要翻译: 公开了将衍生的含炔烃类似物作为细胞糖缀合物的“标签”的代谢寡糖工程方法。 将炔基衍生的Fuc和炔基衍生的ManNAc糖掺入细胞糖缀合物中。 公开了包含叠氮基和视觉或荧光探针并用于标记炔衍生的糖标记的糖缀合物的化学探针。 化学探针通过Cu(I)催化的[3 + 2]叠氮炔环加成与炔基共价结合,并在细胞表面,细胞内或细胞提取物中显现。 标记的糖缀合物能够通过流式细胞术,SDS-PAGE,Western印迹,ELISA,共聚焦显微镜和质谱检测。

    Reishi F3 sub fraction polysaccharides and methods of using same
    39.
    发明授权
    Reishi F3 sub fraction polysaccharides and methods of using same 有权
    Reishi F3分级多糖及其使用方法

    公开(公告)号:US08071105B2

    公开(公告)日:2011-12-06

    申请号:US12244709

    申请日:2008-10-02

    IPC分类号: A61K36/06

    摘要: The present disclosure relates to the discovery of methods of isolating subfractions of an F3 Reishi extract, and of administration of these novel isolates to eukaryotic cells in order to induce certain immumodulatory, hematopoeitic and tumor-inhibiting phenotypic changes in those eukaryotic cells, mediated through particular toll-like receptor (TLR) and other transmembrane receptors. F3 subfractions F301 and F331 have demonstrated that F331 is capable of activating at least TLR-2 while F301 is capable of activating at least TLR-2, TLR-4, and TLR-5.

    摘要翻译: 本公开涉及发现分离F3赖氏提取物的亚组分的方法,以及将这些新型分离物施用于真核细胞,以便诱导那些通过特异性介导的那些真核细胞中的某些免疫调节,造血细胞和肿瘤抑制表型变化 toll样受体(TLR)和其他跨膜受体。 F3亚分数F301和F331已经证明F331能够至少激活至少TLR-2,而F301能够至少激活TLR-2,TLR-4和TLR-5。

    Methods and reagents for the analysis and purification of polysaccharides
    40.
    发明授权
    Methods and reagents for the analysis and purification of polysaccharides 有权
    用于多糖分析和纯化的方法和试剂

    公开(公告)号:US07998482B2

    公开(公告)日:2011-08-16

    申请号:US12533086

    申请日:2009-07-31

    摘要: The disclosure provides fusion proteins comprising a carbohydrate recognition domain of an innate immunity receptor and a heterologous polypeptide. The fusion proteins of the disclosure may be used, for example, to fingerprint polysaccharide compositions and to purify polysaccharide compositions. Polysaccharide compositions include those isolated from Ganoderma lucidum (Reishi). The methods and reagents of the disclosure may also be used to identify innate immunity receptors and cell types that bind to polysaccharide compositions (including polysaccharide compositions associated with pathogens), whereupon modulators of the identified receptors can then be obtained. The fusion proteins also may be used to inhibit the interaction between a polysaccharide composition and an innate immunity receptor on a cell surface. The methods and reagents of the disclosure are used in one example to determine that the DLVR1 innate immunity receptor on macrophages interacts with Dengue virus (DV), and that DLVR1 is responsible for DV-mediated secretion of proinflammatory cytokines from macrophages. The disclosure also provides DVLR1 antibodies that prevent the secretion of proinflammatory cytokines by DV-infected macrophages.

    摘要翻译: 本公开提供了包含先天免疫受体的碳水化合物识别结构域和异源多肽的融合蛋白。 本公开的融合蛋白可以用于例如指纹多糖组合物和纯化多糖组合物。 多糖组合物包括从灵芝(Reishi)分离的那些。 本公开的方法和试剂也可用于鉴定结合多糖组合物(包括与病原体相关的多糖组合物)的先天免疫受体和细胞类型,于是可以获得鉴定的受体的调节剂。 融合蛋白也可用于抑制多糖组合物和细胞表面上的先天免疫受体之间的相互作用。 在一个实例中使用本公开的方法和试剂来确定巨噬细胞上的DLVR1先天免疫受体与登革热病毒(DV)相互作用,并且DLVR1负责来自巨噬细胞的DV介导的促炎细胞因子的分泌。 本公开还提供DVLR1抗体,其防止DV感染的巨噬细胞分泌促炎细胞因子。