CN108135181A - 定新型抗生素及相关组合物的方法 - Google Patents
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- C—CHEMISTRY; METALLURGY
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
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- C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
- C12Q1/37—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
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- C—CHEMISTRY; METALLURGY
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- C12Y—ENZYMES
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- C12Y—ENZYMES
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- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| US201562214695P | 2015-09-04 | 2015-09-04 | |
| US62/214,695 | 2015-09-04 | ||
| PCT/US2016/049869 WO2017040762A2 (en) | 2015-09-04 | 2016-09-01 | Methods for identifying novel antibiotics and related compositions |
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| CA (1) | CA2997530A1 (https=) |
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| US20200181101A1 (en) * | 2017-07-05 | 2020-06-11 | The Scripps Research Institute | Benzamide inhibitors of bacterial lipoprotein signal peptidase |
| EP3587382A1 (en) * | 2018-06-28 | 2020-01-01 | Rheinische Friedrich-Wilhelms-Universität Bonn | Click-mass spectrometry of alkyne-labeled compounds |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62236494A (ja) * | 1986-04-08 | 1987-10-16 | Sumitomo Chem Co Ltd | シグナルペプチダ−ゼに対するモノクロ−ナル抗体、およびそれを産生するハイブリド−マ |
| WO1991009952A1 (en) * | 1989-12-26 | 1991-07-11 | Majesty (Her) In Right Of Canada As Represented By The National Research Council Of Canada | Lipoprotein signal peptide fused to antigenic polypeptides |
| US20090215106A1 (en) * | 2005-09-05 | 2009-08-27 | Iris Pribilla | Method for detecting intracellular interaction between biomolecules |
| CN101855361A (zh) * | 2007-10-10 | 2010-10-06 | 奇华顿股份有限公司 | 酶促方法和酶 |
| US7888005B2 (en) * | 2003-02-12 | 2011-02-15 | The Curators Of The University Of Missouri | Inhibitors of macromolecular activity |
| US20130012687A1 (en) * | 2009-09-21 | 2013-01-10 | The Board Of Trustees Of The Leland Stanford Junior University | Inducible self-cleaving protease tag and method of purifying recombinant proteins using the same |
| CN103502466A (zh) * | 2010-09-07 | 2014-01-08 | 斯隆－凯特林纪念癌症中心 | 用于γ-分泌酶测定的方法和组合物 |
| WO2014096821A1 (en) * | 2012-12-18 | 2014-06-26 | Isis Innovation Limited | Detection of membrane proteins |
| US20140287447A1 (en) * | 2013-03-14 | 2014-09-25 | Ronald R. Fiscus | Ultrasensitive methodology for quantifying the kinase catalytic activity of any protein kinase in biological/clinical samples or recombinant/purified proteins using near-infrared-fluorescence (NIRF)-labeled, kinase-selective peptide substrates and a combination of kinase-selective inhibitors to define individual kinase activity |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0724051D0 (en) * | 2007-12-08 | 2008-01-16 | Medical Res Council | Mutant proteins and methods for producing them |
| EP2612916A1 (en) * | 2012-01-09 | 2013-07-10 | Universität Zürich | Cellular high throughput encapsulation for screening or selection |
| JP6327662B2 (ja) * | 2012-09-26 | 2018-05-23 | 学校法人藤田学園 | 細胞表面タンパクを抗原とする抗体を測定する方法 |
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2016
- 2016-09-01 CA CA2997530A patent/CA2997530A1/en not_active Abandoned
- 2016-09-01 CN CN201680058081.8A patent/CN108135181A/zh active Pending
- 2016-09-01 EP EP16842970.2A patent/EP3344043A4/en not_active Withdrawn
- 2016-09-01 WO PCT/US2016/049869 patent/WO2017040762A2/en not_active Ceased
- 2016-09-01 JP JP2018511420A patent/JP2018532384A/ja active Pending
- 2016-09-01 US US15/756,741 patent/US20190144912A1/en not_active Abandoned
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62236494A (ja) * | 1986-04-08 | 1987-10-16 | Sumitomo Chem Co Ltd | シグナルペプチダ−ゼに対するモノクロ−ナル抗体、およびそれを産生するハイブリド−マ |
| WO1991009952A1 (en) * | 1989-12-26 | 1991-07-11 | Majesty (Her) In Right Of Canada As Represented By The National Research Council Of Canada | Lipoprotein signal peptide fused to antigenic polypeptides |
| US7888005B2 (en) * | 2003-02-12 | 2011-02-15 | The Curators Of The University Of Missouri | Inhibitors of macromolecular activity |
| US20090215106A1 (en) * | 2005-09-05 | 2009-08-27 | Iris Pribilla | Method for detecting intracellular interaction between biomolecules |
| CN101855361A (zh) * | 2007-10-10 | 2010-10-06 | 奇华顿股份有限公司 | 酶促方法和酶 |
| US20130012687A1 (en) * | 2009-09-21 | 2013-01-10 | The Board Of Trustees Of The Leland Stanford Junior University | Inducible self-cleaving protease tag and method of purifying recombinant proteins using the same |
| CN103502466A (zh) * | 2010-09-07 | 2014-01-08 | 斯隆－凯特林纪念癌症中心 | 用于γ-分泌酶测定的方法和组合物 |
| WO2014096821A1 (en) * | 2012-12-18 | 2014-06-26 | Isis Innovation Limited | Detection of membrane proteins |
| US20140287447A1 (en) * | 2013-03-14 | 2014-09-25 | Ronald R. Fiscus | Ultrasensitive methodology for quantifying the kinase catalytic activity of any protein kinase in biological/clinical samples or recombinant/purified proteins using near-infrared-fluorescence (NIRF)-labeled, kinase-selective peptide substrates and a combination of kinase-selective inhibitors to define individual kinase activity |
Non-Patent Citations (6)
| Title |
|---|
| CLAUDIA WITKE 等: "Cloning and nucleotide sequence of the signal peptidase II (lsp)-gene from Staphylococcus carnosus", 《FEMS MICROBIOLOGY LETTERS》 * |
| FUJIO YU 等: "Nucleotide sequence of the lspA gene, the structural gene for lipoprotein signal peptidase of Escherichia coli", 《FEBS LETTERS》 * |
| YAMADA H 等: "The major outer membrane lipoprotein and new lipoproteins share a common signal peptidase that exists in the cytoplasmic membrane of Escherichia coli", 《FEBS LETTERS》 * |
| YAMAGATA 等: "Cloning and expression of a gene coding for the prolipoprotein signal peptidase of Escherichia coli, Federation of European Biochemical Societies", 《FEBS LETTERS》 * |
| 主编：苏式兵 等: "《生命科学前沿技术与中医药研究》", 30 September 2013, 上海浦江教育出版社 * |
| 田锦: "《基因操作技术》", 31 August 2013, 中国农业大学出版社 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2017040762A2 (en) | 2017-03-09 |
| JP2018532384A (ja) | 2018-11-08 |
| CA2997530A1 (en) | 2017-03-09 |
| US20190144912A1 (en) | 2019-05-16 |
| EP3344043A2 (en) | 2018-07-11 |
| EP3344043A4 (en) | 2019-07-10 |
| WO2017040762A3 (en) | 2017-07-13 |
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