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    • 1. 发明申请
    • METHODS AND COMPOSITIONS FOR THE TREATMENT OR PREVENTION OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION
    • 治疗或预防人类免疫缺陷病毒感染的方法和组合
    • US20090232831A1
    • 2009-09-17
    • US12338987
    • 2008-12-18
    • Chi-Huey WongSheng-Kai WangPi-Hui Liang
    • Chi-Huey WongSheng-Kai WangPi-Hui Liang
    • A61K39/42A61K31/715C07H1/00C12Q1/70
    • A61K31/715A61K39/00G01N33/56988G01N33/6854G01N2400/00G01N2500/04
    • A conserved cluster of oligomannose glycans on gp120 has been identified as the epitope recognized by the broadly HIV-1-neutralizing monoclonal antibody 2G12. Oligomannose glycans are also the ligands for DC-SIGN, a C-type lectin found on the surface of dendritic cells. Multivalency is fundamental for carbohydrate-protein interactions, and mimicking of the high glycan density on the virus surface has become essential for designing carbohydrate-based HIV vaccines and antiviral agents. Synthesis of oligomannose dendrons, which display multivalent oligomannoses in high density, and characterize their interaction with 2G12 and DC-SIGN by a glycan microarray binding assay is disclosed. These glycodendrons inhibit the binding of gp120 to 2G12 and recombinant dimeric DC-SIGN with IC50 in the nanomolar range. A second-generation Man9 dendron was identified as a potential immunogen for HIV vaccine development and as a potential antiviral agent.
    • 已经鉴定了gp120上寡聚糖单糖聚糖的保守簇,被广泛的HIV-1中和单克隆抗体2G12识别为表位。 寡聚甘露糖聚糖也是DC-SIGN的配体,DC-SIGN是树突细胞表面上发现的C型凝集素。 多值是碳水化合物 - 蛋​​白质相互作用的基础,并且模仿病毒表面上的高聚糖密度对于设计基于碳水化合物的HIV疫苗和抗病毒剂已变得至关重要。 公开了通过聚糖微阵列结合测定法显示高密度多价寡糖单糖的寡甘露糖树突的合成,并表征其与2G12和DC-SIGN的相互作用。 这些甘草酮抑制gp120与2G12的结合和重组二聚体DC-SIGN,其IC50在纳摩尔范围。 第二代Man9树突被鉴定为HIV疫苗开发的潜在免疫原,并被认为是潜在的抗病毒剂。
    • 6. 发明授权
    • Quantitative microarray of intact glycolipid CD1d interaction and correlation with cell-based cytokine production
    • 完整糖脂CD1d相互作用的定量微阵列和与细胞因子生成的相关性
    • US08383554B2
    • 2013-02-26
    • US12423728
    • 2009-04-14
    • Chi-Huey WongPi-Hui Liang
    • Chi-Huey WongPi-Hui Liang
    • C40B60/00C40B40/12C07G3/00
    • C40B30/04C40B40/12G01N2333/70539G01N2405/10
    • The protein CD1d binds self and foreign glycolipids for presentation to CD1-restricted T cells by means of TCR recognition, and activates TH1 and TH2 chemokines release. Accordingly, a variety of glycolipid ligands were attached to a microarray surface and their binding with CD1d investigated. An α-galactosyl ceramide (α-GalCer) bearing a carbamate group at the 6′-OH position was tethered to the surface and the dissociation constant with CD1d determined. Competition assays were used to determine the dissociation constants (Ki) of the new and intact glycolipids. The para-fluoroheptaphenyl-modified α-GalCer was found to bind most strongly with CD1d (Ki 0.14 μM), two orders of magnitude stronger than α-GalCer and more than three times more selective for IFN-γ release. Various α-GalCer analogs were analyzed and the results showed that the binding affinity of glycolipids to CD1d correlates well with IFN-γ production, but poorly with IL-4 secretion by NKT cells, suggesting that tighter binding ligands could bias cytokine release through the TH1 pathway.
    • 蛋白质CD1d通过TCR识别结合自身和外来糖脂呈递给CD1限制性T细胞,并激活TH1和TH2趋化因子释放。 因此,将各种糖脂配体连接到微阵列表面,并研究它们与CD1d的结合。 在6'-OH位置带有氨基甲酸酯基的α-半乳糖神经酰胺(α-GalCer)被固定在表面,测定了CD1d的解离常数。 使用竞争测定来确定新的和完整的糖脂的解离常数(Ki)。 发现对 - 氟苯哌啶修饰的α-GalCer与CD1d(Ki0.14μM)最强结合,比α-GalCer强两个数量级,对于IFN-γ释放是选择性的三倍以上。 分析各种α-GalCer类似物,结果表明,糖脂对CD1d的结合亲和力与IFN-γ产生良好相关,但与NKT细胞的IL-4分泌差异较小,表明更严格的结合配体可能通过TH1偏置细胞因子释放 途径。
    • 9. 发明申请
    • QUANTITATIVE MICROARRAY OF INTACT GLYCOLIPID CD1D INTERACTION AND CORRELATION WITH CELL-BASED CYTOKINE PRODUCTION
    • 定量微晶玻璃纤维素CD1D相互作用和与细胞因子生产的相关性
    • US20090275483A1
    • 2009-11-05
    • US12423728
    • 2009-04-14
    • Chi-Huey WongPi-Hui Liang
    • Chi-Huey WongPi-Hui Liang
    • C40B30/04C40B40/12
    • C40B30/04C40B40/12G01N2333/70539G01N2405/10
    • The protein CD1d binds self and foreign glycolipids for presentation to CD1-restricted T cells by means of TCR recognition, and activates TH1 and TH2 chemokines release. Accordingly, a variety of glycolipid ligands were attached to a microarray surface and their binding with CD1d investigated. An α-galactosyl ceramide (α-GalCer) bearing a carbamate group at the 6′-OH position was tethered to the surface and the dissociation constant with CD1d determined. Competition assays were used to determine the dissociation constants (Ki) of the new and intact glycolipids. The para-fluoroheptaphenyl-modified α-GalCer was found to bind most strongly with CD1d (Ki 0.14 μM), two orders of magnitude stronger than α-GalCer and more than three times more selective for IFN-γ release. Various α-GalCer analogs were analyzed and the results showed that the binding affinity of glycolipids to CD1d correlates well with IFN-γ production, but poorly with IL-4 secretion by NKT cells, suggesting that tighter binding ligands could bias cytokine release through the TH1 pathway.
    • 蛋白质CD1d通过TCR识别结合自身和外来糖脂呈递给CD1限制性T细胞,并激活TH1和TH2趋化因子释放。 因此,将各种糖脂配体连接到微阵列表面,并研究它们与CD1d的结合。 在6'-OH位置带有氨基甲酸酯基团的α-半乳糖神经酰胺(α-GalCer)被束缚于表面,并且确定了CD1d的解离常数。 使用竞争测定来确定新的和完整的糖脂的解离常数(Ki)。 发现对 - 氟苯哌啶修饰的α-GalCer与CD1d(Ki0.14μM)最强结合,比α-GalCer强两个数量级,对于IFN-γ释放是选择性的三倍以上。 分析各种α-GalCer类似物,结果表明,糖脂对CD1d的结合亲和力与IFN-γ产生良好相关,但与NKT细胞的IL-4分泌差异较小,表明更紧密的结合配体可能通过TH1偏置细胞因子释放 途径。