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    Glycan conjugates and methods of use thereof
    61.
    发明授权
    Glycan conjugates and methods of use thereof 有权

    公开(公告)号：US10342858B2

    公开(公告)日：2019-07-09

    申请号：US14832993

    申请日：2015-08-21

    Applicant: Academia Sinica

    Inventor： Chi-Huey Wong ,  Chung-Yi Wu

    IPC: C07H5/02 ,  C07H5/04 ,  C07H5/06 ,  A61K39/00 ,  C07H15/04 ,  C07H15/26 ,  C07K16/30 ,  C07K16/44 ,  C08B37/00 ,  A61K31/715 ,  A61K31/7028

    Abstract: The present disclosure is directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA3/SSEA4/GloboH associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globo-series glycosphingolipid synthesis. The present disclosure relates to methods and compositions which can modulate the globo-series glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globo-series glycosphingolipid SSEA3/SSEA4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globo-series synthetic pathway. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions.

    CANCER MARKERS AND METHODS OF USE THEREOF
    69.
    发明申请
    CANCER MARKERS AND METHODS OF USE THEREOF 审中-公开
    癌症标记及其使用方法

    公开(公告)号：US20160274121A1

    公开(公告)日：2016-09-22

    申请号：US15005930

    申请日：2016-01-25

    Applicant: Academia Sinica

    Inventor： Chi-Huey Wong ,  Chung-Yi Wu ,  Sarah K.C. Cheung ,  Po-Kai Chuang ,  Tsui-Ling Hsu

    IPC: G01N33/574 ,  C07K16/30

    CPC classification number: G01N33/57492 ,  A61K2039/505 ,  C07K16/18 ,  C07K16/3053 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/622 ,  C07K2317/734 ,  C07K2317/92 ,  G01N33/5073 ,  G01N33/57407 ,  G01N2333/70585 ,  G01N2333/70596 ,  G01N2405/10 ,  G01N2500/04 ,  G01N2500/10 ,  G01N2800/52

    Abstract: The present disclosure relates to methods and compositions which can modulate the globoseries glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globoseries glycosphingolipid SSEA-3/SSEA-4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globoseries synthetic pathway. Additionally, the present disclosure is also directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA-3/SSEA-4/GLOBO H associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globoseries glycosphingolipid synthesis. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions. Furthermore, the instant disclosure also relates to cancer stem cell biomarkers for disgnostic and therapeutic uses.

    Abstract translation: 本公开涉及可以调节球形蛋白糖鞘脂合成的方法和组合物。 特别地，本公开涉及可以调节生物合成途径中的球形蛋白鞘糖脂SSEA-3 / SSEA-4 / GloboH的合成的糖酵母抑制剂化合物及其组合物和使用方法; 特别是糖酵解抑制剂靶向α-4GalT; β-4GalNAcT-I; 或β-3GalT-V酶在球形蛋白合成途径中。 另外，本公开还涉及靶向SSEA-3 / SSEA-4 / GLOBO H相关表位（天然和修饰）的疫苗，抗体和/或免疫原性缀合物组合物，其引发可用于调节的抗体和/或结合片段产生 全球糖苷脂蛋白合成。 此外，本公开还涉及使用本文所述的组合物治疗或检测过度增殖性疾病和/或病症的方法。 此外，本公开还涉及用于预后和治疗用途的癌症干细胞生物标志物。

    CRYSTAL STRUCTURE OF BIFUNCTIONAL TRANSGLYCOSYLASE PBP1B FROM E. COLI AND INHIBITORS THEREOF
    70.
    发明申请
    CRYSTAL STRUCTURE OF BIFUNCTIONAL TRANSGLYCOSYLASE PBP1B FROM E. COLI AND INHIBITORS THEREOF 有权
    来自大肠杆菌及其抑制剂的双功能转移酶PBP1B的晶体结构

    公开(公告)号：US20160083337A1

    公开(公告)日：2016-03-24

    申请号：US14960025

    申请日：2015-12-04

    Applicant: Academia Sinica

    Inventor： Chi-Huey Wong ,  Che Alex Ma ,  Ting-Jen Rachel Cheng ,  Wei-Chieh Cheng

    IPC: C07C235/64 ,  C07C235/84

    CPC classification number: C07C235/64 ,  C07C235/84 ,  C07K2299/00 ,  C12Q1/18 ,  C12Q1/48 ,  G01N2333/91102 ,  G01N2500/00

    Abstract: The crystal structure at 2.16 Å resolution of the full-length bacterial bifunctional transglycosylase penicillin-binding protein 1b (PBP1b) from Escherichia coli, in complex with its inhibitor moenomycin, is provided. The atomic coordinates of the complex as well as the moenomycin binding site are provided. Three dimensional structures of amino acid residues involved in moenomycin binding and transglycosylation activity are identified. Binding site for peptidoglycan synthesis inhibitors comprising inhibitor-binding site comprises amino acid residues from at least one of transglycosylase (TG), UvrB domain 2 homolog (UB2H) and transmembrane (TM) domains of PBP1b are identified at an atomic level of resolution. Methods for rational drug design based on the atomic coordinates are provided. Methods for screening for antibiotics based on anisotropic binding assay and transglycosylase inhibitor assays are provided. Novel antibiotics based on the screening assays of the invention are disclosed.

    Abstract translation: 提供了与其抑制剂新霉素复合的大肠杆菌全长细菌双功能转糖苷酶青霉素结合蛋白1b（PBP1b）的分辨率为2.16的晶体结构。 提供复合物的原子坐标以及霉酚霉素结合位点。 鉴定了涉及霉酚霉素结合和转糖基化活性的氨基酸残基的三维结构。 包含抑制剂结合位点的肽聚糖合成抑制剂的结合位点包含以分辨率的原子级别鉴定的来自转糖苷酶（TG），UvrB结构域2同源物（UB2H）和跨膜（TM）结构域中的至少一种的氨基酸残基。 提供了基于原子坐标的合理药物设计方法。 提供了基于各向异性结合测定法和转糖苷酶抑制剂测定法筛选抗生素的方法。 公开了基于本发明筛选试验的新型抗生素。

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