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1. 发明授权

US09034576B2 Systems and methods for measuring translation of target proteins in cells 有权
标题翻译：用于测量细胞中靶蛋白翻译的系统和方法
公开(公告)号：US09034576B2
公开(公告)日：2015-05-19
申请号：US13497273
申请日：2010-09-21
申请人： Zeev Smilansky , Barry S. Cooperman , Yale E. Goodman
发明人： Zeev Smilansky , Barry S. Cooperman , Yale E. Goodman
IPC分类号： C12Q1/68 , G01N33/50 , G01N33/542
CPC分类号： G01N21/6428 , G01N33/5023 , G01N33/542 , G01N2201/061
摘要： The present invention relates to systems and methods for measuring the rate of translation of a target protein in cells, which are based on the detection of translation of one or more predetermined codon pairs during synthesis of the target protein. The detection is provided by a FRET signal emitted from labeled tRNA molecules which are juxtaposed during synthesis of the protein.
摘要翻译：本发明涉及用于测量细胞中靶蛋白的翻译速率的系统和方法，其基于在靶蛋白合成期间检测一个或多个预定密码子对的翻译。该检测由在蛋白质合成期间并置的标记的tRNA分子发射的FRET信号提供。

2. 发明申请

US20120183957A1 SYSTEMS AND METHODS FOR MEASURING TRANSLATION OF TARGET PROTEINS IN CELLS 有权
标题翻译：用于测量细胞中目标蛋白翻译的系统和方法
公开(公告)号：US20120183957A1
公开(公告)日：2012-07-19
申请号：US13497273
申请日：2010-09-21
申请人： Zeev Smilansky , Barry S. Cooperman , Yale E. Goodman
发明人： Zeev Smilansky , Barry S. Cooperman , Yale E. Goodman
IPC分类号： G01N21/64
CPC分类号： G01N21/6428 , G01N33/5023 , G01N33/542 , G01N2201/061
摘要： The present invention relates to systems and methods for measuring the rate of translation of a target protein in cells, which are based on the detection of translation of one or more predetermined codon pairs during synthesis of the target protein. The detection is provided by a FRET signal emitted from labeled tRNA molecules which are juxtaposed during synthesis of the protein.
摘要翻译：本发明涉及用于测量细胞中靶蛋白的翻译速率的系统和方法，其基于在靶蛋白合成期间检测一个或多个预定密码子对的翻译。该检测由在蛋白质合成期间并置的标记的tRNA分子发射的FRET信号提供。

3. 发明授权

US08785119B2 Fluorescent labeling of transfer RNA and study of protein synthesis 有权
标题翻译：转染RNA的荧光标记和蛋白质合成研究
公开(公告)号：US08785119B2
公开(公告)日：2014-07-22
申请号：US12664952
申请日：2008-06-20
申请人： Barry S. Cooperman , Zeev Smilansky , Yale E. Goldman , Dongli Pan
发明人： Barry S. Cooperman , Zeev Smilansky , Yale E. Goldman , Dongli Pan
IPC分类号： C12Q1/68 , C07H21/00
CPC分类号： G01N33/582 , C12P19/34 , C12P21/02 , C12Q1/6806 , G01N33/5308 , G01N33/6803
摘要： Provided are methods for labeling transfer RNA comprising replacing the uracil component of a dihydrouridine of said transfer RNA with a fluorophore. The disclosed methods may comprise fluorescent labeling of natural tRNAs (i.e., tRNAs that have been synthesized in a cell, for example, in a bacterium, a yeast cell, or a vertebrate cell) at dihydrouridine (D) positions, or fluorescent labeling of synthetic tRNAs. In another aspect, the present invention provides methods for assessing protein synthesis in a translation system comprise providing a tRNA having a fluorophore substitution for the uracil component of a dihydrouridine in a D loop of the tRNA; introducing the labeled tRNA into the translation system; irradiating the translation system with electromagnetic radiation, thereby generating a fluorescence signal from the fluorophore; detecting the fluorescence signal; and, correlating the fluorescence signal to one or more characteristics of the protein synthesis in the translation system. The disclosed methods are useful in single molecule as well as in ensemble settings.
摘要翻译：提供用于标记转移RNA的方法，包括用荧光团替代所述转移RNA的二氢尿苷的尿嘧啶组分。所公开的方法可以包括在二氢尿苷（D）位置处天然tRNA（即在细胞中例如细菌，酵母细胞或脊椎动物细胞中合成的tRNA）的荧光标记，或合成的荧光标记 tRNA。另一方面，本发明提供了用于评估翻译系统中的蛋白质合成的方法，包括在tRNA的D环中提供具有二氢尿苷的尿嘧啶组分的荧光团取代的tRNA; 将标记的tRNA引入翻译系统; 用电磁辐射照射翻译系统，从而产生来自荧光团的荧光信号; 检测荧光信号; 并将荧光信号与翻译系统中蛋白质合成的一个或多个特征相关联。所公开的方法在单分子以及整体设置中是有用的。

4. 发明申请

US20110262899A1 FLUORESCENT LABELING OF TRANSFER RNA AND STUDY OF PROTEIN SYNTHESIS 有权
标题翻译：转染RNA的荧光标记和蛋白质合成研究
公开(公告)号：US20110262899A1
公开(公告)日：2011-10-27
申请号：US12664952
申请日：2008-06-20
申请人： Barry S. Cooperman , Zeev Smilansky , Yale E. Goldman , Dongli Pan
发明人： Barry S. Cooperman , Zeev Smilansky , Yale E. Goldman , Dongli Pan
IPC分类号： C12Q1/68 , C07H21/02
CPC分类号： G01N33/582 , C12P19/34 , C12P21/02 , C12Q1/6806 , G01N33/5308 , G01N33/6803
摘要： Provided are methods for labeling transfer RNA comprising replacing the uracil component of a dihydrouridine of said transfer RNA with a fluorophore. The disclosed methods may comprise fluorescent labeling of natural tRNAs (i.e., tRNAs that have been synthesized in a cell, for example, in a bacterium, a yeast cell, or a vertebrate cell) at dihydrouridine (D) positions, or fluorescent labeling of synthetic tRNAs. In another aspect, the present invention provides methods for assessing protein synthesis in a translation system comprise providing a tRNA having a fluorophore substitution for the uracil component of a dihydrouridine in a D loop of the tRNA; introducing the labeled tRNA into the translation system; irradiating the translation system with electromagnetic radiation, thereby generating a fluorescence signal from the fluorophore; detecting the fluorescence signal; and, correlating the fluorescence signal to one or more characteristics of the protein synthesis in the translation system. The disclosed methods are useful in single molecule as well as in ensemble settings.
摘要翻译：提供用于标记转移RNA的方法，包括用荧光团替代所述转移RNA的二氢尿苷的尿嘧啶组分。所公开的方法可以包括在二氢尿苷（D）位置处天然tRNA（即在细胞中例如细菌，酵母细胞或脊椎动物细胞中合成的tRNA）的荧光标记，或合成的荧光标记 tRNA。另一方面，本发明提供了用于评估翻译系统中的蛋白质合成的方法，包括在tRNA的D环中提供具有二氢尿苷的尿嘧啶组分的荧光团取代的tRNA; 将标记的tRNA引入翻译系统; 用电磁辐射照射翻译系统，从而产生来自荧光团的荧光信号; 检测荧光信号; 并将荧光信号与翻译系统中蛋白质合成的一个或多个特征相关联。所公开的方法在单分子以及整体设置中是有用的。

5. 发明授权

US5266465A .alpha.-1-antichymotrypsin, analogues and methods of production 失效
标题翻译： α-1抗胰凝乳蛋白酶，类似物和生产方法
公开(公告)号：US5266465A
公开(公告)日：1993-11-30
申请号：US735322
申请日：1991-07-24
申请人： Harvey Rubin , Zhi M. Wang , Barry S. Cooperman , Norman Schecter
发明人： Harvey Rubin , Zhi M. Wang , Barry S. Cooperman , Norman Schecter
IPC分类号： A61K38/00 , C07K14/81 , C07K3/00 , A61K45/05 , C12N15/09 , C12P21/02
CPC分类号： C07K14/8125 , A61K38/00
摘要： The invention provides .alpha.-1-antichymotrypsin and protein preparations comprising human .alpha.-1-antichymotrypsin produced by E. coli cells transformed with a DNA sequence encoding human .alpha.-1-antichymotrypsin. The invention also provides methods for producing .alpha.-1-antichymotrypsin. The invention further provides analogues of .alpha.-1-antichymotrypsin that exhibit antichymotrypsin, anti-trypsin and anti-thrombin activity and methods of producing the analogues.
摘要翻译：本发明提供了包含用编码人α1-抗胰凝乳蛋白酶的DNA序列转化的大肠杆菌细胞产生的人α1-抗胰凝乳蛋白酶的α-1抗胰凝乳蛋白酶和蛋白质制剂。本发明还提供了生产α-1抗胰凝乳蛋白酶的方法。本发明还提供表现出抗胰凝乳蛋白酶，抗胰蛋白酶和抗凝血酶活性的α-1-抗胰凝乳蛋白酶的类似物和产生类似物的方法。

6. 发明授权

US6030942A Peptides peptide analogs peptidomimetics and other small molecules useful for inhibiting the activity of ribonucleotide reductase 失效
标题翻译：肽肽类似物肽模拟物和其他可用于抑制核糖核苷酸还原酶活性的小分子
公开(公告)号：US6030942A
公开(公告)日：2000-02-29
申请号：US40216
申请日：1998-03-17
申请人： Barry S. Cooperman , Ralph F. Hirschmann , Amos B. Smith, III , Paul Laub , Setsuya Sasho , Paul A. Sprengeler , Bari A. Barwis , Alison Fisher , Shrikumar Nair
发明人： Barry S. Cooperman , Ralph F. Hirschmann , Amos B. Smith, III , Paul Laub , Setsuya Sasho , Paul A. Sprengeler , Bari A. Barwis , Alison Fisher , Shrikumar Nair
IPC分类号： A61K38/00 , C12N9/02 , A61K38/12 , A61K38/16
CPC分类号： C12N9/0093 , A61K38/00
摘要： The invention relates to compositions which are useful for inhibiting ribonucleotide reductase enzymes, including the mammalian ribonucleotide reductase enzyme. The compositions include, but are not limited to, linear peptides, cyclic peptides, peptide analogs, and peptidomimetics. Methods of using the compositions of the invention to treat cancer and viral and bacterial infections are disclosed.
摘要翻译：本发明涉及可用于抑制核糖核苷酸还原酶（包括哺乳动物核糖核苷酸还原酶）的组合物。组合物包括但不限于线性肽，环肽，肽类似物和肽模拟物。公开了使用本发明组合物治疗癌症和病毒和细菌感染的方法。

7. 发明授权

US5723316A .alpha.-1-antichymotrypsin analogues having chymase inhibiting activity 失效
标题翻译：具有糜酶抑制活性的α-1抗胰凝乳蛋白酶类似物
公开(公告)号：US5723316A
公开(公告)日：1998-03-03
申请号：US221171
申请日：1994-03-31
申请人： Barry S. Cooperman , Harvey Rubin , Norman Schechter , Zhi Mei Wang
发明人： Barry S. Cooperman , Harvey Rubin , Norman Schechter , Zhi Mei Wang
IPC分类号： C12N15/09 , A61K38/00 , A61K38/55 , A61P7/02 , A61P9/00 , A61P29/00 , A61P31/04 , C07H21/04 , C07K14/81 , C12N1/21 , C12N5/10 , C12N9/99 , C12P21/02 , C12R1/19 , C12N15/00 , A61K38/43
CPC分类号： C07K14/8121 , C07K14/8125 , A61K38/00
摘要： The invention provides analogues of .alpha.-1-antichymotrypsin having amino acid substitutions at position 358. .alpha.-1-antichymotrypsin analogues having amino acid substitutions at positions 356-361 and analogues having amino acid substitutions at positions 356-361 wherein the amino acid at position 358 is substituted are also within the scope of the invention. These analogues exhibit chymase inhibitory activity. Also provided are novel .alpha.-1-antichymotrypsins having an N-terminal extension of methionine-alanine-serine or alanine-serine. Expression vectors for the production of .alpha.-1-antichymotrypsins are also provided. The present invention also provides host cells and cell cultures capable of expressing analogues of .alpha.-1-antichymotrypsin, as well as protein preparations from the host cells. Methods of producing and using the analogues of .alpha.-1-antichymotrypsin to inhibit chymase activity are also provided.
摘要翻译：本发明提供了在358位具有氨基酸取代的α-1-抗胰凝乳蛋白酶的类似物。在356-361位具有氨基酸取代的α1-抗胰凝乳蛋白酶类似物和在位置356-361处具有氨基酸取代的类似物，其中位置处的氨基酸 358也在本发明的范围内。这些类似物表现出糜酶抑制活性。还提供了具有甲硫氨酸 - 丙氨酸 - 丝氨酸或丙氨酸 - 丝氨酸的N-末端延伸的新型α-1抗胰凝乳蛋白。还提供了用于产生α-1抗胰凝乳蛋白的表达载体。本发明还提供能够表达α-1-胰凝乳蛋白酶类似物的宿主细胞和细胞培养物，以及来自宿主细胞的蛋白质制剂。还提供了产生和使用α-1抗胰凝乳蛋白酶类似物以抑制胃促胰酶活性的方法。

8. 发明授权

US5674708A .alpha.-1-antichymotrypsin analogues having elastase inhibitory activity 失效
标题翻译：具有弹性蛋白酶抑制活性的α-1抗胰凝乳蛋白酶类似物
公开(公告)号：US5674708A
公开(公告)日：1997-10-07
申请号：US221078
申请日：1994-03-31
申请人： Barry S. Cooperman , Harvey Rubin , Norman Schechter , Zhi Mei Wang
发明人： Barry S. Cooperman , Harvey Rubin , Norman Schechter , Zhi Mei Wang
IPC分类号： C12N15/09 , A61K31/00 , A61K38/00 , A61K38/55 , A61P1/00 , A61P11/00 , A61P13/02 , A61P15/00 , A61P29/00 , A61P31/04 , A61P43/00 , C07H21/04 , C07K14/81 , C12N1/21 , C12N9/99 , C12P21/02 , C12R1/19 , C12N15/15
CPC分类号： C07K14/8121 , C07K14/8125 , A61K38/00
摘要： The present invention provides an analogue of human .alpha.-1-antichymotrypsin wherein the amino acid at position 358 is selected from the group consisting of isoleucine, valine, alanine, aspattic acid, threonine, and glutamic acid.
摘要翻译：本发明提供人α1-抗胰凝乳蛋白酶的类似物，其中位置358处的氨基酸选自异亮氨酸，缬氨酸，丙氨酸，天冬氨酸，苏氨酸和谷氨酸。

9. 发明授权

US5367064A .alpha.-1-antichymotrypsin, analogues and methods of production 失效
标题翻译： α-1抗胰凝乳蛋白酶，类似物和生产方法
公开(公告)号：US5367064A
公开(公告)日：1994-11-22
申请号：US5908
申请日：1993-01-15
申请人： Harvey Rubin , Zhi M. Wang , Barry S. Cooperman , Norman Schechter
发明人： Harvey Rubin , Zhi M. Wang , Barry S. Cooperman , Norman Schechter
IPC分类号： A61K38/00 , C07K14/81 , C07H21/04 , C07K13/00 , C12N15/22
CPC分类号： C07K14/8125 , A61K38/00
摘要： The invention provides .alpha.-1-antichymotrypsin and protein preparations comprising human .alpha.-1-antichymotrypsin produced by E. coli cells transformed with a DNA sequence encoding human .alpha.-1-antichymotrypsin. The invention also provides methods for producing .alpha.-1-antichymotrypsin. The invention further provides analogues of .alpha.-1-antichymotrypsin that exhibit antichymotrypsin, anti-trypsin and anti-thrombin activity and methods of producing the analogues.
摘要翻译：本发明提供了包含用编码人α1-抗胰凝乳蛋白酶的DNA序列转化的大肠杆菌细胞产生的人α1-抗胰凝乳蛋白酶的α-1抗胰凝乳蛋白酶和蛋白质制剂。本发明还提供了生产α-1抗胰凝乳蛋白酶的方法。本发明还提供表现出抗胰凝乳蛋白酶，抗胰蛋白酶和抗凝血酶活性的α-1-抗胰凝乳蛋白酶的类似物和产生类似物的方法。

10. 发明授权

US5459063A Plasmodium falciparum ribonucleotide reductase DNA 失效
标题翻译：恶性疟原虫核糖核苷酸还原酶DNA
公开(公告)号：US5459063A
公开(公告)日：1995-10-17
申请号：US136743
申请日：1993-10-14
申请人： Barry S. Cooperman , Harvey Rubin , Jerome Salem , Alison L. Fisher
发明人： Barry S. Cooperman , Harvey Rubin , Jerome Salem , Alison L. Fisher
IPC分类号： A61K38/00 , C07K14/445 , C12N9/02 , C12N15/53
CPC分类号： C12N9/0093 , C07K14/445 , A61K38/00
摘要： This invention relates to the ribonucleotide reductase of Plasmodium falciparum (Pf RR), to the subunits of Pf RR (Pf R1 and Pf R2), and to compounds comprising peptides derived from the Pf R2 C-terminus sequence that inhibit the action of protozoal RR. The invention provides a method for the prevention and treatment of malaria caused by P. falciparum by controlling the proliferation of P. falciparum comprising administering to a patient at least one peptide according to the invention. Antimalarial compositions are provided which comprise a pharmaceutically acceptable carrier and at least one peptide according to the invention which inhibits the P. falciparum ribonucleotide reductase reduction of ribonucleotides to 2'-deoxyribonucleotides. Also provided are methods for diagnosing malaria and for screening potential antimalarial agents.
摘要翻译：本发明涉及恶性疟原虫（Pf RR）对Pf RR（Pf R1和Pf R2）的亚基的核糖核苷酸还原酶，以及包含抑制原生动物RR作用的Pf R2 C-末端序列的肽的化合物。本发明提供了通过控制恶性疟原虫的增殖来预防和治疗由恶性疟原虫引起的疟疾的方法，其包括向患者施用至少一种本发明的肽。提供了抗疟组合物，其包含药学上可接受的载体和根据本发明的至少一种肽，其将核糖核苷酸的恶性疟原虫核糖核苷酸还原酶还原成2'-脱氧核糖核苷酸。还提供了诊断疟疾和筛选潜在抗疟药物的方法。

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