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1. 发明申请

WO2021113989A1 METHOD OF DIAGNOSING AND TREATMENT MONITORING OF CROHN'S DISEASE AND ULCERATIVE COLITIS 审中-公开
公开(公告)号：WO2021113989A1
公开(公告)日：2021-06-17
申请号：PCT/CA2020/051717
申请日：2020-12-13
申请人： MCMASTER UNIVERSITY
发明人： BRITZ-MCKIBBIN, Philip , PAI, Nikhil
IPC分类号： G01N33/48 , G01N33/483 , G01N33/487 , G01N33/493 , G01N33/53
摘要： Methods of diagnosing Crohn's disease and ulcerative colitis in subjects is provided based on the determination of metabolites in urine samples, such as serine, hypoxanthine, kynurenine, threonine, dimethylglycine, tryptophan, indoxylsulfate, phenylacetylglutamine, sialic acid, 5-hydroxy-6-indolyl-o-sulfate, 5-(Δ-carboxybutyl) homocysteine, and/or an anion having m/z:RMT:polarity of 345.1553:0.770:n, or determination of metabolites in stool samples, such as ketodeoxycholic acid, cholic acid, choline, tryptophan, trimethyllysine, serine, butyric acid, lactic acid, hypoxanthine and/or guanine.

2. 发明申请

WO2016109899A1 ALLOSTERIC ACTIVATORS FOR TREATMENT OF PHENYLKETONURIA 审中-公开
标题翻译：用于治疗苯丙酮的单药激活剂
公开(公告)号：WO2016109899A1
公开(公告)日：2016-07-14
申请号：PCT/CA2016/050017
申请日：2016-01-08
申请人： MCMASTER UNIVERSITY
发明人： BRITZ-MCKIBBIN, Philip
IPC分类号： A61K31/192 , A61K31/519 , A61K47/48 , A61P3/00 , C07C62/04 , C07C62/32 , C12Q1/00 , C12Q1/26
CPC分类号： A61K31/215 , A61K31/19 , A61K31/191 , A61K31/192 , A61K31/519 , A61K38/51 , A61P3/00 , A61P43/00 , C12Q1/00 , C12Q1/26 , C12Y114/16001 , A61K2300/00
摘要： A method of restoring activity in phenylalanine hydroxylase is provided. The method comprises exposing the phenylalanine hydroxylase to shikimic acid, a functionally equivalent analogue thereof, a pharmaceutically acceptable salt of shikimic acid or analogue thereof, or combinations thereof, A method of screening for allosteric activators for a target enzyme is also provided comprising the steps of: denaturing the target enzyme with a first chaotropic agent to yield denatured enzyme, incubating the denatured enzyme with a candidate compound under denaturing conditions to allow enzyme refolding, and assaying enzyme activity in the presence of enzyme substrate and a candidate compound; and if enzyme activity of the denatured enzyme was restored in step i) by at least about 10% of residual enzyme activity, denaturing the target enzyme with a second chaotropic agent to yield denatured enzyme, incubating the denatured enzyme with the candidate compound under non-denaturing conditions to allow enzyme refolding, and assaying enzyme activity in the presence of enzyme substrate and the candidate compound, wherein an increase in enzyme activity of at least about 10% of residual enzyme activity indicates that the candidate compound is an allosteric activator of the target enzyme.
摘要翻译：提供了恢复苯丙氨酸羟化酶活性的方法。该方法包括将苯丙氨酸羟化酶暴露于莽草酸，其功能上等同的类似物，莽草酸或其类似物的药学上可接受的盐或其组合。还提供筛选靶酶的变构激活剂的方法，包括以下步骤：：用第一离液剂变性目标酶以产生变性酶，在变性条件下将变性酶与候选化合物孵育以允许酶重折叠，并在酶底物和候选化合物存在下测定酶活性; 并且如果在步骤i）中将变性酶的酶活性恢复至少约10％的残留酶活性，则用第二离液剂对目标酶进行变性以产生变性酶，将变性酶与候选化合物在非 - 变性条件以允许酶重折叠，以及在酶底物和候选化合物存在下测定酶活性，其中酶活性的增加至少为残余酶活性的约10％表明候选化合物是靶的变构激活剂酶。

3. 发明申请

WO2014183217A1 MULTI-SEGMENT INJECTION-CAPILLARY ELECTROPHORESIS-MASS SPECTROMETRY (MSI-CE-MS): A MULTIPLEXED SCREENING PLATFORM AND DATA WORKFLOW FOR CHEMICAL ANALYSIS 审中-公开
标题翻译：多部门注射 - 电泳 - 质谱（MSI-CE-MS）：化学分析的多层筛选平台和数据工作流程
公开(公告)号：WO2014183217A1
公开(公告)日：2014-11-20
申请号：PCT/CA2014/050454
申请日：2014-05-14
申请人： MCMASTER UNIVERSITY
发明人： BRITZ-MCKIBBIN, Philip
IPC分类号： G01N27/447
CPC分类号： G01N27/44782 , G01N27/447 , G01N27/4473 , G01N27/44743 , G01N30/7266 , H01J49/0027 , H01J49/0404 , H01J49/165
摘要： Various embodiments illustrating a multiplexed method for high throughput screening of ions in biological samples within a single capillary when using capillary electrophoresis mass spectrometry (CE-MS) are illustrated. The method includes sequential injection of multiple sample segments in series within a single capillary, the sample segments being separated by a spacer plug of buffer, and multiplexed analysis of the sample segments simultaneously within a single capillary electrophoresis (CE) run. The method also includes application of voltage to the single capillary subsequent to sequential injection and zonal separation of polar metabolites within each sample segment by CE such that each analyte zone migrates within its characteristic electrophoretic mobility offset in time by the spacer. The incorporation of a quality control/reference sample and the use of dilution patterning with specific injection configurations also enables encoding of information temporally for enhanced data processing with quality assurance.
摘要翻译：示出了当使用毛细管电泳质谱（CE-MS）时，单个毛细管内的生物样品中离子生物样品的高通量筛选的多路复用方法。该方法包括在单个毛细管内连续注射多个样品片段，样品片段由缓冲液的间隔塞隔开，并在单个毛细管电泳（CE）运行中同时对样品片段进行多重分析。该方法还包括在CE之间顺序注射和每个样品区段内的极性代谢物的区域分离之后，向单个毛细管施加电压，使得每个分析物区域在其特征电泳迁移率偏移期间通过间隔物在时间上迁移。质量控制/参考样品的并入以及使用具有特定注射配置的稀释图案化也可以使信息在时间上进行编码，从而提高质量保证的数据处理能力。

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