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1. 发明申请

WO2012118900A3 SURFACE DISPLAY OF CELLULOLYTIC ENZYMES AND ENZYME COMPLEXES ON GRAM-POSITIVE MICROORGANISMS 审中-公开
标题翻译：纤维素酶和酶复合物在革兰氏阳性微生物上的表面展示
公开(公告)号：WO2012118900A3
公开(公告)日：2012-11-29
申请号：PCT/US2012027150
申请日：2012-02-29
申请人： UNIV CALIFORNIA , CLUBB ROBERT T , ANDERSON TIMOTHY
发明人： CLUBB ROBERT T , ANDERSON TIMOTHY
IPC分类号： C12N1/21 , C12N15/31 , C12N15/52 , C12N15/74 , C12P19/12
CPC分类号： C12Q1/34 , C12N1/22 , C12N9/2437 , C12P19/02 , C12P19/14
摘要： In various embodiments a system is provided that displays heterologous proteins on the surface of a Gram-positive microorganism. In certain embodiments the system displays proteins using a sortase transpeptidase to covalently anchor proteins to the cell wall of the microbe. Novel bacterial strains are provided to exploit this system to display cellulase enzymes and multi-enzyme complexes on the surface of Gram-positive microorganisms (e.g., Bacillus subtilis) through their non-covalent interaction with a scaffoldin protein that is covalently anchored to the cell wall by the sortase transpeptidase. The surface displayed protein complexes contain enzymes capable of degrading cellulose into its component sugars at accelerated rates as compared to solutions of purified enzymes.
摘要翻译：在各种实施方案中，提供了在革兰氏阳性微生物的表面上展示异源蛋白质的系统。在某些实施方案中，系统使用分选酶转肽酶展示蛋白质以将蛋白质共价锚定至微生物的细胞壁。提供了新的细菌菌株以利用该系统通过它们与共价锚定到细胞壁的支架蛋白的非共价相互作用在革兰氏阳性微生物（例如枯草芽孢杆菌）的表面上展示纤维素酶和多酶复合物由分选酶transpeptidase。与纯化酶的溶液相比，表面展示的蛋白质复合物含有能够以加速的速率将纤维素降解为其组分糖的酶。

2. 发明申请

WO2011028492A2 SORTASE A INHIBITORS 审中-公开
标题翻译：输入一个抑制剂
公开(公告)号：WO2011028492A2
公开(公告)日：2011-03-10
申请号：PCT/US2010046394
申请日：2010-08-23
申请人： UNIV CALIFORNIA , JUNG MICHAEL E , CLUBB ROBERT T , YI SUNG WOOK , SUREE NUTTEE , CLEMENS JEREMY JUSTIN
发明人： JUNG MICHAEL E , CLUBB ROBERT T , YI SUNG WOOK , SUREE NUTTEE , CLEMENS JEREMY JUSTIN
IPC分类号： A61K31/501
CPC分类号： C07D237/12 , C07D231/18 , C07D231/26 , C07D237/14 , C07D237/18 , C07D277/32 , C07D277/34 , C07D277/36 , C07D417/06
摘要： Bacterial infections, including Methicillin resistant Staphylococcus aureus (MRSA) infections are a major health problem that has created a pressing need for new antibiotics. Pyridazinone, rhodanine, and pyrazolethione compounds effective inhibit the enzymatic activity of sortase A (srtA) found in gram positive bacteria are disclosed. A structure activity relationship (SAR) analysis led to the identification of several pyridazinone and pyrazolethione analogs that inhibit SrtA with IC50 values in the sub-micromolar range. Compounds that inhibit the S. aureus SrtA sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. Many of these molecules also inhibit the sortase enzyme from B. anthracis suggesting that they may be generalized sortase inhibitors. The novel compounds, compositions, uses, formulations, medicaments, articles of manufacture provide improved materials, uses, and treatments useful in combating infectious disorders.
摘要翻译：细菌感染，包括耐甲氧西林金黄色葡萄球菌（MRSA）感染是一个主要的健康问题，迫切需要新的抗生素。公开了有效抑制革兰氏阳性细菌中分泌酶A（srtA）的酶活性的哒嗪酮，绕丹宁和吡唑硫酮化合物。结构活动关系（SAR）分析导致了几种抑制SrtA的哒嗪酮和吡唑硫酮类似物的鉴定，其IC50值在亚微摩尔范围内。抑制金黄色葡萄球菌SrtA分选酶的化合物可以作为有效的抗感染剂起作用，因为该酶将毒力因子附着在细胞壁上。这些分子中的许多还抑制炭疽杆菌分选酶，表明它们可以是广义分解酶抑制剂。新型化合物，组合物，用途，制剂，药物，制品提供改善的材料，用途和用于对抗传染病的治疗。

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