公开(公告)号：US08507660B2

公开(公告)日：2013-08-13

申请号：US12749118

申请日：2010-03-29

Applicant: Chi-Huey Wong ,  Ting-Jen Rachel Cheng ,  Chung-Yi Wu

Inventor： Chi-Huey Wong ,  Ting-Jen Rachel Cheng ,  Chung-Yi Wu

IPC: C07H1/00 ,  C07H5/06 ,  C07H7/04 ,  C07H9/06 ,  C40B30/04 ,  C40B50/00 ,  C40B40/12

CPC classification number: A61K39/095 ,  C07H1/00 ,  C07H3/00 ,  C07H9/06 ,  C07H11/00 ,  C07H11/04 ,  C07H13/04

Abstract: A novel N-acetyl-5-N,4-O-carbonyl-protected dibutyl sialyl phosphate donor for sialylation of both primary and sterically hindered secondary acceptors to prepare sialosides with high yield and α-selectivity is disclosed. Methods for making disaccharide building blocks comprising α(2→3), α(2→6), α(2→8), α(2→8)/α(2→9) alternate, and α(2→9) sialosides are provided. methods for one-pot synthesis of complex sialosides are disclosed. Libraries of sialosides and methods for using the libraries for detection and receptor binding analysis of surface glycoproteins or pathogens and cancer cells are disclosed. Methods for distinguishing between hemagglutinin (HA) from various strains of influenza are provided.

Abstract translation: 公开了一种新型N-乙酰基-5-N，4-O-羰基保护的二丁基唾液酸磷酸供体，用于主要和空间位阻次级受体的唾液酸化，以高产率和α-选择性制备唾液酸苷。 制备包含α（2-> 3），α（2-> 6），α（2-> 8），α（2-> 8）/α（2-> 9）的二糖结构单元的方法交替， （2-> 9）唾液酸苷。 公开了一锅合成唾液酸苷的方法。 公开了唾液酸的文库和使用文库进行表面糖蛋白或病原体和癌细胞的检测和受体结合分析的方法。 提供了用于区分来自各种流感病毒的血凝素（HA）的方法。

公开(公告)号：US20100121107A1

公开(公告)日：2010-05-13

申请号：US12506982

申请日：2009-07-21

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

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

IPC: C12Q1/48 ,  C07C233/75

CPC classification number: C07C235/64 ,  C07C235/84 ,  C07K2299/00 ,  C12Q1/18 ,  C12Q1/48 ,  G01N33/573 ,  G01N2333/91102 ,  G01N2500/00 ,  G01N2500/04 ,  G01N2500/20

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。