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1. 发明申请

WO2006047514A2 DAPH ANALOGS AND INHIBITION OF PROTEIN AGGREGATION 审中-公开
标题翻译： DAPH类似物和蛋白质聚集的抑制
公开(公告)号：WO2006047514A2
公开(公告)日：2006-05-04
申请号：PCT/US2005/038358
申请日：2005-10-25
申请人： WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH , MASSACHUSETTS INSTITUTE FOR TECHNOLOGY , INGRAM, Vernon , BUCHWALD, Stephen, L. , HENNESSY, Edward , LINDQUIST, Susan , SHORTER, James , STEELE, Andrew , DUENNWALD, Martin
发明人： INGRAM, Vernon , BUCHWALD, Stephen, L. , HENNESSY, Edward , LINDQUIST, Susan , SHORTER, James , STEELE, Andrew , DUENNWALD, Martin
IPC分类号： A61K31/4035
CPC分类号： C07D209/48
摘要： The invention relates to compounds which inhibit aggregation of proteins of peptides, or disaggregate protein aggregates, and thereby antagonize the toxic effects of such aggregates. The invention also relates to methods for using such compounds and methods for discovering compounds that inhibit protein or peptide aggregation.
摘要翻译：本发明涉及抑制肽的蛋白质聚集或分解蛋白质聚集体并由此拮抗这些聚集体的毒性作用的化合物。本发明还涉及使用这些化合物的方法和用于发现抑制蛋白质或肽聚集的化合物的方法。

2. 发明申请

WO2005118633A2 ELECTRICAL CONDUCTORS AND DEVICES FROM PRION-LIKE PROTEINS 审中-公开
标题翻译：电导体和来自类似蛋白质的器件
公开(公告)号：WO2005118633A2
公开(公告)日：2005-12-15
申请号：PCT/US2005/017870
申请日：2005-05-20
申请人： THE WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH , LINDQUIST, Susan , SHORTER, James , SCHEIBEL, Thomas
发明人： LINDQUIST, Susan , SHORTER, James , SCHEIBEL, Thomas
IPC分类号： C07K14/47
CPC分类号： C07K14/47 , C07K14/39 , C07K14/395 , C07K2319/21
摘要： The present invention provides novel polypeptides comprising a prionaggregation domain and a second domain; novel polynucleotides encoding such polypeptides; host cells transformed or transfected with such polynucleotides; novel fibrils with specific functionalities and unusually high chemical and thermal stability; and methods of making and using the foregoing.
摘要翻译：本发明提供了包含朊病毒聚集域和第二结构域的新型多肽; 编码这种多肽的新型多核苷酸; 用这种多核苷酸转化或转染的宿主细胞; 具有特定功能的新颖纤维和异常高的化学和热稳定性; 以及制作和使用前述的方法。

3. 发明申请

WO2010111516A3 COMPOSITIONS AND METHODS FOR INHIBITING BIOFILMS 审中-公开
公开(公告)号：WO2010111516A3
公开(公告)日：2010-09-30
申请号：PCT/US2010/028703
申请日：2010-03-25
申请人： WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH , LINDQUIST, Susan , KRISHNAN, Rajaraman
发明人： LINDQUIST, Susan , KRISHNAN, Rajaraman
IPC分类号： C07K14/425 , C07K7/06 , C07K7/08 , C07K16/12 , A61K38/00 , A61K39/40 , A61P31/04 , G01N33/68
摘要： Using arrays of peptides derived from E. coli CsgB, peptides that seed formation of curli fibers are identified. The arrays, peptides, methods for identification thereof, and compositions and methods relating thereto, are provided.

4. 发明申请

WO2012154858A1 CHAPERONE INTERACTION ASSAYS AND USES THEREOF 审中-公开
标题翻译： CHAPERONE相互作用测定及其用途
公开(公告)号：WO2012154858A1
公开(公告)日：2012-11-15
申请号：PCT/US2012/037131
申请日：2012-05-09
申请人： WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH , TAIPALE, Mikko , LINDQUIST, Susan
发明人： TAIPALE, Mikko , LINDQUIST, Susan
IPC分类号： G01N33/53 , G01N33/547 , G01N33/543 , G01N33/487
CPC分类号： G01N33/573 , C12Q1/485 , C12Q1/66 , G01N33/502 , G01N33/54306 , G01N33/57484 , G01N33/6845 , G01N33/6872 , G01N2500/02 , G01N2800/60
摘要： In some aspects, the invention provides methods of identifying, detecting, and/or measuring protein-protein interactions. In some aspects, the invention provides methods of identifying and/or characterizing modulators of protein-protein interactions. In some aspects, the invention provides methods of identifying and/or characterizing modulators of protein activity, wherein the methods are based at least in part on measuring interaction between a chaperone and client protein. In some aspects, the invention provides methods for identifying and/or characterizing compounds and/or for assessing compound specificity, wherein the methods are based at least in part on measuring interaction between a chaperone and client protein. In some embodiments, a client protein is a kinase. In some embodiments, a compound is a kinase inhibitor. In some aspects, the invention provides methods of profiling kinase inhibitor specificity. In some aspects, the invention provides assay systems and/or reagents useful for performing one or more of the inventive methods. In some aspects, the invention provides newly identified targets of a variety of kinase inhibitors. In some aspect, the invention provides methods of inhibiting kinases identified herein as targets of certain kinase inhibitors. In some aspects, the invention provides methods of treating a disease, e.g., cancer, by inhibiting one or more kinase(s) newly identified as targets of certain kinase inhibitors.
摘要翻译：在一些方面，本发明提供鉴定，检测和/或测量蛋白质 - 蛋白质相互作用的方法。在一些方面，本发明提供鉴定和/或表征蛋白质 - 蛋白质相互作用调节剂的方法。在一些方面，本发明提供鉴定和/或表征蛋白质活性调节剂的方法，其中所述方法至少部分地基于测量分子伴侣和客体蛋白质之间的相互作用。在一些方面，本发明提供用于鉴定和/或表征化合物和/或用于评估化合物特异性的方法，其中所述方法至少部分地基于测量伴侣和客体蛋白之间的相互作用。在一些实施方案中，客户蛋白质是激酶。在一些实施方案中，化合物是激酶抑制剂。在一些方面，本发明提供了分析激酶抑制剂特异性的方法。在一些方面，本发明提供了用于执行本发明方法中的一种或多种的测定系统和/或试剂。在一些方面，本发明提供了新鉴定的各种激酶抑制剂的靶标。在一些方面，本发明提供了抑制本文鉴定的激酶作为某些激酶抑制剂靶标的方法。在一些方面，本发明提供了通过抑制新鉴定为某些激酶抑制剂的靶标的一种或多种激酶来治疗疾病例如癌症的方法。

5. 发明申请

WO2011014693A2 BACTERIOPHAGES EXPRESSING AMYLOID PEPTIDES AND USES THEREOF 审中-公开
标题翻译：表达淀粉样肽的噬菌体及其用途
公开(公告)号：WO2011014693A2
公开(公告)日：2011-02-03
申请号：PCT/US2010/043770
申请日：2010-07-29
申请人： WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH , TRUSTEES OF BOSTON UNIVERSITY , LU, Timothy Kuan-Ta , LINDQUIST, Susan , KRISHNAN, Rajaraman , COLLINS, James , O'DONNELL, Charles W , LEIGHTON, Bonnie Berger , DEVADAS, Srinivas
发明人： LU, Timothy Kuan-Ta , LINDQUIST, Susan , KRISHNAN, Rajaraman , COLLINS, James , O'DONNELL, Charles W , LEIGHTON, Bonnie Berger , DEVADAS, Srinivas
IPC分类号： C12N15/63 , C12N15/12 , C12N7/01 , C07K14/47 , A61K38/17 , A61P25/28
CPC分类号： C07K14/4711 , A61K35/76 , A61K38/00 , C07K2319/735 , C12N2795/10232 , C12N2795/10243 , C12N2795/14132 , C12N2795/14143 , Y02A50/475 , A61K2300/00
摘要： The present invention generally relates to engineered bacteriophages which express amyloid peptides for the modulation (e.g. increase or decrease) of protein aggregates and amyloid formation. In some embodiments, the engineered bacteriophages express anti-amyloid peptides for inhibiting protein aggregation and amyloid formation, which can be useful in the treatment and prevention of and bacterial infections and biofilms. In some embodiments, the engineered bacteriophages express amyloid peptides for promoting amyloid formation, which are useful for increasing amyloid formation such as promoting bacterial biofilms. Other aspects relate to methods to inhibit bacteria biofilms, and methods for the treatment of amyloid related disorders, e.g., Alzheimer's disease using an anti-amyloid peptide engineered bacteriophages. Other aspects of the invention relate to engineered bacteriophages to express the amyloid peptides on the bacteriophage surface and/or secrete the amyloid peptides, e.g., anti-amyloid peptides and pro-amyloid peptides, and uses thereof for modulating protein aggregates and amyloid formation.
摘要翻译：本发明一般涉及表达淀粉样蛋白肽用于调节（例如增加或减少）蛋白质聚集体和淀粉样蛋白形成的工程化噬菌体。在一些实施方案中，工程改造的噬菌体表达用于抑制蛋白质聚集和淀粉样蛋白形成的抗淀粉样肽，其可用于治疗和预防细菌感染和生物膜。在一些实施方案中，工程改造的噬菌体表达促淀粉样蛋白形成的淀粉样肽，其可用于增加淀粉样蛋白形成，例如促进细菌生物膜。其它方面涉及抑制细菌生物膜的方法，以及使用抗淀粉样肽工程改造的噬菌体治疗淀粉样蛋白相关病症例如阿尔茨海默病的方法。本发明的其它方面涉及在噬菌体表面上表达淀粉样肽和/或分泌淀粉样肽（例如抗淀粉样肽和淀粉样前肽）的工程化噬菌体，以及其用于调节蛋白质聚集体和淀粉样蛋白形成的用途。 / p>

6. 发明申请

WO2006135738A2 DEVICES FROM PRION-LIKE PROTEINS 审中-公开
标题翻译：从类似蛋白质的设备
公开(公告)号：WO2006135738A2
公开(公告)日：2006-12-21
申请号：PCT/US2006/022460
申请日：2006-06-09
申请人： THE WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH , LINDQUIST, Susan , KRISHMAN, Rajaraman , TESSIER, Peter
发明人： LINDQUIST, Susan , KRISHMAN, Rajaraman , TESSIER, Peter
IPC分类号： C07K14/47
CPC分类号： C07K14/4711
摘要： The present invention provides novel polypeptides comprising a prion- aggregation domain and a second domain; novel polynucleotides encoding such polypeptides; host cells transformed or transfected with such polynucleotides; novel fibrils with specific functionalities and unusually high chemical and thermal stability; and methods of making and using the foregoing in, for example, the production of nanoscale devices.
摘要翻译：本发明提供了包含朊病毒聚集域和第二结构域的新型多肽; 编码这种多肽的新型多核苷酸; 用这种多核苷酸转化或转染的宿主细胞; 具有特定功能的新颖纤维和异常高的化学和热稳定性; 以及在例如纳米级器件的制造中制造和使用前述的方法。

7. 发明申请

WO2008033451A3 PROTEIN AGGREGATION DOMAINS FROM PRIONS AND METHODS OF USE THEREOF 审中-公开
公开(公告)号：WO2008033451A3
公开(公告)日：2008-03-20
申请号：PCT/US2007/019910
申请日：2007-09-13
申请人： WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH , LINDQUIST, Susan , TESSIER, Peter
发明人： LINDQUIST, Susan , TESSIER, Peter
IPC分类号： C07K14/39 , C07K14/40 , C07K14/47 , G01N33/68
摘要： Using the Sup35 prion proteins of two distantly related yeast species, it is established that prion replication is initiated by small elements of primary sequence, which can be identified using arrays of short peptides. Subtle differences in replication elements govern the formation of distinct aggregate conformations (prion strains) and also determine their species-specific seeding activities. A Sup35 chimera that promiscuously forms prions in more than one species does so by virtue of carrying the replication element of each species. Mutations or conditions that cause the chimera to assemble into distinct prion strains favor recognition of distinct replication elements. Therefore, subtle differences in small sequences that constitute prion replication elements encode important determinants of prion propagation and transmission. The protein aggregation domains, methods for identification thereof, and polypeptides and higher order aggregates including the protein interaction domains, as well as arrays including peptides derived from an aggregation-prone polypeptide are provided.

8. 发明申请

WO2017106367A8 METHOD OF TREATING NEURODEGENERATIVE DISORDERS BY RESCUING ALPHA-SYNUCLEIN TOXICITY 审中-公开
公开(公告)号：WO2017106367A8
公开(公告)日：2017-06-22
申请号：PCT/US2016/066687
申请日：2016-12-14
申请人： D.E. SHAW RESEARCH, LLC , WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH , SHAN, Yibing , MYSORE, Venkat , LINDQUIST, Susan , TARDIFF, Dan , CHANDRAMOULI, Srividya
发明人： SHAN, Yibing , MYSORE, Venkat , LINDQUIST, Susan , TARDIFF, Dan , CHANDRAMOULI, Srividya
IPC分类号： A61K31/53 , C07D251/40
摘要： A method for treating neurodegenerative disease in a subject in need thereof by administering to the subject an effective amount of a Nedd4 activator as described herein.

9. 发明申请

WO2017106367A1 METHOD OF TREATING NEURODEGENERATIVE DISORDERS BY RESCUING ALPHA-SYNUCLEIN TOXICITY 审中-公开
标题翻译：治疗神经退行性疾病的方法通过恢复α-SYNUCLEIN毒性
公开(公告)号：WO2017106367A1
公开(公告)日：2017-06-22
申请号：PCT/US2016/066687
申请日：2016-12-14
申请人： D.E. SHAW RESEARCH, LLC , WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH , SHAN, Yibing , MYSORE, Venkat , LINDQUIST, Susan , TARDIFF, Dan , CHANDRAMOULI, Srividya
发明人： SHAN, Yibing , MYSORE, Venkat , LINDQUIST, Susan , TARDIFF, Dan , CHANDRAMOULI, Srividya
IPC分类号： A61K31/53 , C07D251/40
CPC分类号： A61K31/5377 , A61K31/496 , A61K31/53
摘要： A method for treating neurodegenerative disease in a subject in need thereof by administering to the subject an effective amount of a Nedd4 activator as described herein.
摘要翻译：通过向受试者施用有效量的本文所述的Nedd4激活剂来治疗有需要的受试者中的神经变性疾病的方法。

10. 发明申请

WO2014022692A1 PRION-BASED MANIPULATION OF YEAST FERMENTATION AND GROWTH 审中-公开
标题翻译： YEAST发酵和成长的基于优势的操作
公开(公告)号：WO2014022692A1
公开(公告)日：2014-02-06
申请号：PCT/US2013/053272
申请日：2013-08-01
申请人： WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH
发明人： JAROSZ, Daniel , BROWN, Jessica, C.S. , LINDQUIST, Susan
IPC分类号： C12N1/16 , C12N15/67 , C07K2/00
CPC分类号： C07K14/395 , C12N1/18 , C12N1/36
摘要： In some aspects, the invention provides methods of modulating yeast fermentation or growth by modulating the [ GAR+ ] prion. In some embodiments, [ GAR+ ] is induced by contacting yeast cells with a bacterium that produces a small molecule inducer of [ GAR+ ] or by contacting yeast cells with the small molecule or conditioned medium comprising the small molecule or a fraction of such medium that comprises the small molecule. In some aspects, the invention provides methods of identifying a modulator of a prion of interest. In some embodiments a methods of identifying a modulator of a prion comprises (a) providing a bacterially conditioned medium; (b) contacting at least one fraction of the bacterially conditioned medium with a non-bacterial cell; and (c) monitoring the cell for alteration of a phenotype assocatied with a prion of interest. In some embodiments the non-bacterial cell is a yeast cell. In some embodiments the prion is [ GAR+ ].
摘要翻译：在一些方面，本发明提供了通过调节[GAR +]朊病毒来调节酵母发酵或生长的方法。在一些实施方案中，通过使酵母细胞与产生[GAR +]的小分子诱导剂的细菌接触或通过使酵母细胞与包含小分子的小分子或条件培养基或这种培养基的一部分接触来诱导[GAR +]，所述小分子或条件培养基包含小分子。在一些方面，本发明提供鉴定感兴趣的朊病毒的调节剂的方法。在一些实施方案中，鉴定朊病毒调节剂的方法包括（a）提供细菌条件培养基; （b）将至少一部分细菌培养基与非细菌细胞接触; 和（c）监测细胞以改变与感兴趣的朊病毒有关的表型。在一些实施方案中，非细菌细胞是酵母细胞。在一些实施方案中，朊病毒是[GAR +]。

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