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    • 2. 发明授权
    • O-glycan inhibitors of selectin mediated inflammation derived from PSGL-1
    • 来自PSGL-1的选择素介导的炎症的O-聚糖抑制剂
    • US6124267A
    • 2000-09-26
    • US63237
    • 1998-04-20
    • Rodger P. McEverRichard D. CummingsKevin L. Moore
    • Rodger P. McEverRichard D. CummingsKevin L. Moore
    • C07K14/705C07K16/28A61K31/70
    • C07K16/2896C07K14/705C07K2317/34
    • Tyrosine sulfate on PSGL-1, particularly at least one of residues 46, 48 and 51, functions in conjunction with sialylated and fucosylated glycans, most preferably Thr-57, to mediate high affinity binding to P-selectin. PSGL-1 O-glycans have been determined to consist of disialylated or neutral forms of the core-2 tetrasaccharide Gal.beta.1.fwdarw.4GlcNAc.beta.1.fwdarw.6(Gal.beta.1.fwdarw.3)GalNAcOH. A minority of the O-glycans are .alpha.1,3 fucosylated that occur as two major species containing the sialyl Lewis x antigen--one species is a disialylated monofucosylated glycan: Fuc.alpha.1 .dwnarw. 3 NeuAc.alpha.2.fwdarw.3Gal.beta.1.fwdarw.4GlcNAc.beta.1 .dwnarw. 6 NeuAc.alpha.2.fwdarw.3Gal.beta.1.fwdarw.3GalNAc-R, and the other is a monosialylated, trifucosylated glycan having a polylactosamine backbone: Fuc.alpha.l .dwnarw. 3 NeuAc.alpha.2.fwdarw.3Gal.beta.1.fwdarw.4GlcNAc.beta.1.fwdarw.3Gal.beta.1.fwdarw. Fuc.alpha.l Fuc.alpha.l .dwnarw. .dwnarw. 3 3 4GlcNAc.beta.1.fwdarw.3Gal.beta.1.fwdarw.4GlcNAc.beta.1 .dwnarw. 6 Gal.beta.1.fwdarw.3GalNAc-R wherein R=H, OH, another sugar or an aglycone such as an amino acid, peptide, or polypeptide. The O-glycans defined herewith can be used to inhibit inflammation mediated by P-selectin.
    • PSGL-1上的酪氨酸硫酸盐,特别是残基46,48和51中的至少一个,与唾液酸化和岩藻糖基化聚糖结合起来,最优选Thr-57,以介导与P-选择素的高亲和力结合。 已经确定PSGL-1 O-聚糖由二核苷酸或中性形式的核心二糖Galβ1-> 4GlcNAcβ1-> 6(Galβ1-> 3)GalNAcOH组成。 少数O聚糖是α1,3-岩藻糖基化的,它们作为含有唾液酸基路易斯x抗原的两种主要物质发生,一种是二唾液酸化单糖基化聚糖: - Fucα1 - &darr& - 3 - NeuAc alpha 2-> 3Gal beta 1-> 4GlcNAc beta 1 - &darr& - 6 - NeuAc alpha 2-> 3Gal beta 1-> 3GalNAc-R, - 另一种是具有多聚乳糖胺骨架的单唾液酸化的三糖基聚糖: - Fucα1 - & alpha 2-> 3Gal beta 1-> 4GlcNAc beta 1-> 3Gal beta 1-> - - Fuc alpha l Fuc alpha l - &darr&&darr& - 3 3 - 4GlcNAc beta 1-> 3Gal beta 1-> 4GlcNAc beta 1 - &darr& 6-Galβ1-> 3GalNAc-R - 其中R = H,OH,另一种糖或糖苷配基如氨基酸,肽或多肽。 本文定义的O-聚糖可用于抑制P-选择素介导的炎症。
    • 9. 发明授权
    • Tyrosylprotein sulfotransferases and methods of use thereof
    • 酪氨酸蛋白磺酸转移酶及其使用方法
    • US06605455B1
    • 2003-08-12
    • US09785343
    • 2001-02-16
    • Kevin L. Moore
    • Kevin L. Moore
    • C12N910
    • C12N9/13C07K14/70596C07K16/40C12Q1/48G01N33/573
    • Tyrosylprotein sulfotransferases and nucleic acids encoding the tyrosyiprotein sulfotransferases are described. Dual isotopes of the enzyme and of the nucleic acids encoding said enzymes have been identified in human, mouse and C. elegans. The polypeptides and polynucleotides exhibit a wide range of homologies. The polynucleotides can be used to transform or transfect host cells for producing substantially pure forms of the enzyme, or for use in an expression system for post-translational tyrosine sulfation of proteins or peptides produced within the expression system. The enzymes can be used to sulfate peptides or proteins requiring sulfation.
    • 描述了酪氨酰蛋白质磺酰转移酶和编码酪氨酸蛋白磺酸转移酶的核酸。 已经在人,小鼠和秀丽隐杆线虫中鉴定了酶和编码所述酶的核酸的双重同位素。 多肽和多核苷酸表现出广泛的同源性。 多核苷酸可用于转化或转染宿主细胞以产生基本上纯的形式的酶,或用于在表达系统内产生的蛋白质或肽的翻译后酪氨酸硫酸化的表达系统中。 酶可用于需要硫酸化的硫酸肽或蛋白质。