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    • 64. 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。
    • 66. 发明申请
    • Glycoproteomic probes for fluorescent imaging of fucosylated glycans in vivo
    • 用于体内岩藻糖基化聚糖荧光成像的糖蛋白质组学探针
    • US20080241856A1
    • 2008-10-02
    • US12079228
    • 2008-03-24
    • Chi-Huey WongTsui-Ling HsuSarah R. HansonMasaaki Sawa
    • Chi-Huey WongTsui-Ling HsuSarah R. HansonMasaaki Sawa
    • G01N33/53C12P19/44C12Q1/00
    • G01N33/582G01N1/30G01N2400/00
    • The disclosure provides a method of labeling of cellular glycans bearing azide groups via a fluorescent labeling technique based on Cu(I)-catalyzed [3+2]cycloaddition (click activation) of a probe comprising an alkynyl group. The method entails generating a fluorescent probe from a nonfluorescent precursor, 4-ethynyl-N-ethyl-1,8-naphthalimide, by Cu(I)-catalyzed [3+2]cycloaddition of the alkyne group of the probe with an azido-modified sugar. The disclosure further provides a method of incorporating an azido-containing fucose analog into glycoconjugates via the fucose salvage pathway. The disclosure provides a method of fluorescent visualization of fucosylated cells by flow cytometry when cells treated with 6-azidofucose are labeled with the click-activated fluorogenic probe or biotinylated alkyne. A method of visualizing the intracellular localization of fucosylated glycoconjugates by fluorescence microscopy is also disclosed.
    • 本公开提供了通过基于包含炔基的探针的Cu(I)催化的[3 + 2]环加成(点击活化)的荧光标记技术来标记携带叠氮基的细胞聚糖的方法。 该方法需要通过Cu(I)催化的[3 + 2]环加成的探针的炔基与非荧光前体4-乙炔基-N-乙基-1,8-萘酰亚胺的生成荧光探针, 改性糖。 本公开进一步提供了通过岩藻糖补救途径将含叠氮基岩藻糖类似物掺入糖缀合物的方法。 本公开内容提供了当用6-叠氮基聚糖处理的细胞用点击激活的荧光探针或生物素化的炔被标记时,流式细胞仪荧光显示岩藻糖基化细胞的方法。 还公开了通过荧光显微镜观察岩藻糖基化糖缀合物的细胞内定位的方法。
    • 68. 发明授权
    • KDO aldolase and condensation reactions employed therewith
    • KDO醛缩酶和与其一起使用的缩合反应
    • US06423834B1
    • 2002-07-23
    • US09247164
    • 1999-02-09
    • Chi-Huey WongTakeshi SugaiGwo-Jenn Shen
    • Chi-Huey WongTakeshi SugaiGwo-Jenn Shen
    • C07H1500
    • C12P19/02C07H7/027C12N9/88C12P7/58C12P9/00Y10S435/822
    • Aureobacterium barkerei strain KDO-37-2 (ATCC 49977) and KDO aldolase (EC 4.1.2.23) isolated therefrom are disclosed. The KDO aldolase is further disclosed to have a broad substrate specificity with respect to its reverse reaction, i.e. the condensation of aldoses with pyruvate to form a wide range of 2-keto-3-deoxy-onic acids, including 2-keto-3-deoxy-nonulosonic acid, 2-keto-3-deoxy-octulosonic acid, 2-keto-3-deoxy-heptulosonic acid, and 2-keto-3-deoxy-hexulosonic acid. In particular, 3-deoxy-D-manno-2-octulosonic acid (D-KDO), a vital component of lipopolysaccharides found in the bacterial outer membrane may be synthesized from D-arabinose and pyruvate in 67% yield. Additionally, protected forms of the KDO aldolase products, e.g. hexaacetyl 2-keto-3-deoxy-nonulosonic acid and pentaacetyl 2-keto-3-deoxy-octulosonic acid, may be decarboxylated to form the corresponding 2-deoxy-aldoses, e.g. 2-deoxy-octulose and 2-deoxy-heptulose respectively.
    • 公开了从其分离的巴氏杆菌菌株KDO-37-2(ATCC 49977)和KDO醛缩酶(EC 4.1.2.23)。 进一步公开KDO醛缩酶相对于其逆反应具有广泛的底物特异性,即醛糖与丙酮酸的缩合形成宽范围的2-酮-3-脱氧ic酸,包括2-酮-3- 脱氧 - 非酮酸,2-酮-3-脱氧 - 八环酮酸,2-酮-3-脱氧 - 庚酮酸和2-酮-3-脱氧 - 己酸。 特别地,在D-细菌外膜中发现的脂多糖的重要组分3-脱氧-D-壬烯-2-辛酮酸(D-KDO)可由D-阿拉伯糖和丙酮酸合成,产率67%。 另外,保护形式的KDO醛缩酶产物,例如, 六乙酰基2-酮-3-脱氧 - 非酮酸和五乙酰基2-酮-3-脱氧 - 八环酸可以脱羧以形成相应的2-脱氧醛糖,例如, 2-脱氧 - 八酮糖和2-脱氧 - 七氟醚。