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1. 发明申请

WO2007100358A3 CONVERGENT SYNTHESIS OF PROTEINS BY KINETICALLY CONTROLLED LIGATION 审中-公开
标题翻译：动力学控制结合法合成蛋白质
公开(公告)号：WO2007100358A3
公开(公告)日：2007-11-22
申请号：PCT/US2006039455
申请日：2006-10-10
申请人： UNIV CHICAGO , KENT STEPHEN B H , BANG DUHEE , PENTELUTE BRAD L , DUREK THOMAS , JOHNSON ERIK
发明人： KENT STEPHEN B H , BANG DUHEE , PENTELUTE BRAD L , DUREK THOMAS , JOHNSON ERIK
IPC分类号： C07K1/02
CPC分类号： C07K1/04 , C07K1/026 , C07K1/067
摘要： The present invention concerns methods and compositions for synthesizing a polypeptide using kinetically controlled reactions involving fragments of the polypeptide for a fully convergent process. In more specific embodiments, a ligation involves reacting a first peptide having a protected cysteyl group at its N-terminal and a phenylthioester at its C-terminal with a second peptide having a cysteine residue at its N-termini and a thioester at its C-termini to form a ligation product. Subsequent reactions may involve deprotecting the cysteyl group of the resulting ligation product and/or converting the thioester into a thiophenylester.
摘要翻译：本发明涉及用于合成多肽的方法和组合物，其使用涉及完整收敛过程的多肽片段的动力学控制反应。在更具体的实施方案中，连接包括使N-末端具有被保护的半胱氨酸基团并且C-末端具有苯硫基酸酯的第一肽与N-末端具有半胱氨酸残基而其C-末端具有硫酯的第二肽反应，末端形成连接产物。随后的反应可能涉及将所得连接产物的半胱氨酸脱保护和/或将硫酯转化为噻吩基酯。

2. 发明申请

WO2007100358A2 CONVERGENT SYNTHESIS OF PROTEINS BY KINETICALLY CONTROLLED LIGATION 审中-公开
标题翻译：通过动态控制的蛋白质合成蛋白质
公开(公告)号：WO2007100358A2
公开(公告)日：2007-09-07
申请号：PCT/US2006/039455
申请日：2006-10-10
申请人： UNIVERSITY OF CHICAGO , KENT, Stephen, B., H. , BANG, Duhee , PENTELUTE, Brad, L. , DUREK, Thomas , JOHNSON, Erik
发明人： KENT, Stephen, B., H. , BANG, Duhee , PENTELUTE, Brad, L. , DUREK, Thomas , JOHNSON, Erik
IPC分类号： C12N15/09 , C07K14/43
CPC分类号： C07K1/04 , C07K1/026 , C07K1/067
摘要： The present invention concerns methods and compositions for synthesizing a polypeptide using kinetically controlled reactions involving fragments of the polypeptide for a fully convergent process. In more specific embodiments, a ligation involves reacting a first peptide having a protected cysteyl group at its N-terminal and a phenylthioester at its C-terminal with a second peptide having a cysteine residue at its N-termini and a thioester at its C-termini to form a ligation product. Subsequent reactions may involve deprotecting the cysteyl group of the resulting ligation product and/or converting the thioester into a thiophenylester.
摘要翻译：本发明涉及使用涉及完全收敛过程的多肽片段的动力学控制反应来合成多肽的方法和组合物。在更具体的实施方案中，连接包括使其N-末端具有被保护的半胱半胱氨酸的第一肽和其C末端的苯硫基酯与其N末端具有半胱氨酸残基的第二肽和其C-末端的硫酯反应，终止形成连接产物。随后的反应可以包括使得到的连接产物的半胱氨酸脱保护和/或将硫酯转化成硫代苯酯。

3. 发明申请

WO1997011958A1 PROTEIN SIGNATURE ANALYSIS 审中-公开
标题翻译：蛋白质标记分析
公开(公告)号：WO1997011958A1
公开(公告)日：1997-04-03
申请号：PCT/US1996015516
申请日：1996-09-27
申请人： THE SCRIPPS RESEARCH INSTITUTE , KENT, Stephen, B., H. , MUIR, Tom, W. , DAWSON, Philip, E. , FITZGERALD, Michael, C.
发明人： THE SCRIPPS RESEARCH INSTITUTE
IPC分类号： C07K01/04
CPC分类号： C07K1/047
摘要： A protein signature analysis is obtained using a peptide ladder library. The molecular signature of a protein is defined to be that subsequence of amino acid positions within the protein which are essential for the protein to bind to a target molecule. The molecular signature may be determined by screening a peptide ladder library which corresponds to the protein against the target molecule. The peptide ladder library is a library of m peptides wherein each peptide has an amino acid sequence of length m corresponding to an amino acid sequence of the protein, with one exception, viz. peptidem has a substitute amino acid at positionm and the substitute amino acid is attached by a labile bond to its neighboring amino acid. Screening the peptide ladder library against the target molecule results in a division of the original mixture into a positive (functional) pool and a negative (non-functional) pool. The pools are separated and subjected to cleavage to obtain cleavage products. Analysis of the cleavage products by mass spectrometry identifies the positions that are essential for the protein to bind to its molecular target.
摘要翻译：使用肽梯图文件获得蛋白质特征分析。蛋白质的分子标记被定义为蛋白质内蛋白质与靶分子结合所必需的氨基酸位置的亚序列。可以通过筛选与靶分子相对应的蛋白质的肽梯形文库来确定分子特征。肽梯形文库是m肽的文库，其中每个肽具有对应于蛋白质的氨基酸序列的长度m的氨基酸序列，除了一个例外，肽在位置具有替代氨基酸，替代氨基酸通过不稳定键连接到其相邻的氨基酸。针对靶分子筛选肽梯形图文库导致原始混合物分为正（功能）池和阴性（非功能）池。将池分离并进行裂解以获得裂解产物。通过质谱分析裂解产物鉴定了蛋白质与其分子靶标结合所必需的位置。

4. 发明申请

WO1993024834A1 METHOD AND PRODUCT FOR THE SEQUENCE DETERMINATION OF PEPTIDES USING A MASS SPECTROMETER 审中-公开
标题翻译：使用质谱仪序列测定肽的方法和产品
公开(公告)号：WO1993024834A1
公开(公告)日：1993-12-09
申请号：PCT/US1993005070
申请日：1993-05-27
申请人： THE ROCKEFELLER UNIVERSITY , CHAIT, Brian, T. , BEAVIS, Ronald , WANG, Rong , KENT, Stephen, B., H.
发明人： THE ROCKEFELLER UNIVERSITY
IPC分类号： G01N33/44
CPC分类号： G01N33/6842 , C07K1/107 , C07K1/128 , G01N33/6824 , Y10T436/24 , Y10T436/25 , Y10T436/255
摘要： Method is described for sequencing polypeptides by forming peptide ladders comprising a series of polypeptides in which adjacent members of the series vary by one amino acid residue and determining the identity and position of each amino acid in the polypeptide by mass spectroscopy.
摘要翻译：描述了通过形成包含一系列多肽的肽梯级来测序多肽的方法，其中该序列的相邻成员变化一个氨基酸残基，并通过质谱确定多肽中每个氨基酸的同一性和位置。

5. 发明申请

WO0219963A3 SYNTHETIC ERYTHROPOIESIS STIMULATING PROTEINS 审中-公开
标题翻译：合成红细胞生成素刺激蛋白
公开(公告)号：WO0219963A3
公开(公告)日：2003-02-06
申请号：PCT/US0121928
申请日：2001-07-12
申请人： GRYPHON THERAPEUTICS INC , KOCHENDOERFER GERD , BOTTI PAOLO , BRADBURNE JAMES A , CHEN SHIAH-YUN , CRESSMAN SONYA , HUNTER CHRISTIE L , KENT STEPHEN B H , LOW DONALD W
发明人： KOCHENDOERFER GERD , BOTTI PAOLO , BRADBURNE JAMES A , CHEN SHIAH-YUN , CRESSMAN SONYA , HUNTER CHRISTIE L , KENT STEPHEN B H , LOW DONALD W
IPC分类号： A61K38/00 , A61K38/02 , A61K38/22 , A61K47/34 , A61K47/42 , A61K47/48 , A61P7/00 , A61P7/06 , A61P9/10 , A61P11/02 , A61P11/06 , A61P17/00 , A61P19/02 , A61P29/00 , A61P31/12 , A61P37/06 , A61P37/08 , A61P43/00 , C07K1/00 , C07K1/06 , C07K14/47 , C07K14/505 , C07K14/52 , C07K17/08 , C07K19/00
CPC分类号： C07K14/505 , A61K38/00
摘要： Synthetic erythropoiesis stimulating proteins are provided. Also provided are methods for synthesizing the proteins. The invention further relates to derivatives of such synthetic erythropoiesis stimulating proteins that are polymer-modified in a defined manner. Methods and uses for such proteins and derivatized proteins are also provided.
摘要翻译：提供合成红细胞生成刺激蛋白。还提供了合成蛋白质的方法。本发明还涉及以定义的方式聚合物修饰的这种合成的红细胞生成刺激蛋白的衍生物。还提供了这些蛋白质和衍生化蛋白质的方法和用途。

6. 发明申请

WO1995004543A1 TEMPLATE ASSEMBLED SYNTHETIC PROTEIN 审中-公开
标题翻译：模板组装合成蛋白
公开(公告)号：WO1995004543A1
公开(公告)日：1995-02-16
申请号：PCT/US1994009165
申请日：1994-08-11
申请人： THE SCRIPPS RESEARCH INSTITUTE , DAWSON, Philip, E. , KENT, Stephen, B., H.
发明人： THE SCRIPPS RESEARCH INSTITUTE
IPC分类号： A61K38/00
CPC分类号： C07K7/02 , C07K1/1077
摘要： A chemoselective ligation approach to the preparation of complex peptides is employed in a simple, convenient synthesis of template-assembled synthetic protein (TASP) molecules. Reaction of readily prepared synthetic pro-helical peptide- alpha COSH molecules, in unprotected form, with a synthetic (BrAc)4template peptide molecule, also in unprotected form, proceeds rapidly in aqueous solution to give a uniform product in high yield. The resulting TASP molecule may be simply purified to homogeneity. Structural homogeneity may be demonstrated by ionspray mass spectrometry. The chemoselective ligation of unprotected peptides represents a general approach to the synthesis of TASP molecules.
摘要翻译：用于制备复合肽的化学选择性连接方法用于简单，方便地合成模板组装的合成蛋白（TASP）分子。容易制备的未保护形式的合成前螺旋肽-αCOSH分子与未保护形式的合成（BrAc）4模板肽分子的反应在水溶液中快速进行，以高产率得到均匀的产物。所得到的TASP分子可以简单地纯化至均匀。结构均匀性可以通过离子喷射质谱法来证明。未保护肽的化学选择性连接代表TASP分子合成的一般方法。

7. 发明申请

WO2004061094A1 WATER-SOLUBLE THIOESTER AND SELENOESTER COMPOUNDS AND METHODS FOR MAKING AND USING THE SAME 审中-公开
标题翻译：水溶性硫醚和硒化合物及其制备和使用方法
公开(公告)号：WO2004061094A1
公开(公告)日：2004-07-22
申请号：PCT/US2003/041542
申请日：2003-12-30
申请人： GRYPHON THERAPEUTICS, INC. , MIRANDA, Leslie, Phillip , KENT, Stephen, B., H.
发明人： MIRANDA, Leslie, Phillip , KENT, Stephen, B., H.
IPC分类号： C12N9/10
CPC分类号： C07K14/001 , C07C327/32 , C07C391/00 , C07K1/04 , C07K1/086 , C07K1/088 , C07K1/10
摘要： Water-soluble thioester and selenoester compounds, their generators, as well as methods for making and using the same, are provided. The subject thioester and selenoester compounds are characterized by including an amino acid synthon having a C-terminal group bonded to a water-soluble polymer through a thioester or selenoester linkage. Solid phase resins and protocols for generating the subject compounds are also provided. The subject water soluble thioester and selenoester compounds and generators find use in a variety of different applications, including thioester or selenoester mediated chemical ligation reactions.
摘要翻译：提供了水溶性硫酯和硒酯化合物，它们的发生剂，以及制备和使用它们的方法。受试者硫酯和硒酯化合物的特征在于包括具有通过硫酯或硒酯连接键合到水溶性聚合物上的C端基的氨基酸合成子。还提供了固相树脂和用于产生本发明化合物的方案。本发明的水溶性硫酯和硒酯化合物和发生器可用于各种不同的应用，包括硫酯或硒酯介导的化学连接反应。

8. 发明申请

WO0012536A2 LIPID MATRIX-ASSISTED CHEMICAL LIGATION AND SYNTHESIS OF MEMBRANE POLYPEPTIDES 审中-公开
标题翻译：脂质基辅助化学合成和膜多糖的合成
公开(公告)号：WO0012536A2
公开(公告)日：2000-03-09
申请号：PCT/US9919542
申请日：1999-08-26
申请人： GRYPHON SCIENCES , KOCHENDOERFER GERD G , HUNTER CHRISTIE L , KENT STEPHEN B H , BOTTI PAOLO
发明人： KOCHENDOERFER GERD G , HUNTER CHRISTIE L , KENT STEPHEN B H , BOTTI PAOLO
IPC分类号： G01N33/532 , A61K49/08 , A61K51/08 , C07C229/16 , C07K1/00 , C07K1/02 , C07K1/04 , C07K1/107 , C07K1/12 , C07K1/13 , C07K14/11 , C07K14/155 , C07K14/16 , C07K14/195 , C07K14/215 , C07K14/36 , C07K14/435 , C07K14/54 , C07K14/705 , C07K17/02 , C07K19/00 , G01N21/78 , G01N33/542 , G01N33/566 , G01N33/68
CPC分类号： A61K49/0056 , A61K49/0041 , C07C229/16 , C07K1/023 , C07K1/026 , C07K1/04 , C07K1/042 , C07K1/045 , C07K14/005 , C07K14/215 , C07K14/36 , C07K14/43522 , C07K14/5421 , C07K14/705 , C07K2319/00 , C12N2740/16322 , C12N2760/16022 , Y10S435/87
摘要： The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis. The methods and compositions of the invention have multiple uses. For example, they can be used to assay ligand binding to membrane polypeptides and domains comprising a receptor, and thus are extremely useful for structure/function studies, drug screening/selection/design, and diagnostics and the like, including high-throughput applications. The methods and compositions of the invention are particularly suited for FRET analyses of previously inaccessible membrane polypeptides.
摘要翻译：本发明涉及掺入脂质基质中的脂质基质辅助化学连接和膜多肽的合成的方法和组合物。本发明通过逐步化学选择性化学连接未受保护的肽区段，其中至少一个肽片段嵌入脂质基质中，制备嵌入脂质基质内的预折叠膜多肽。可以使用适用于未保护肽段连接的任何化学选择性反应化学物质。合适的脂质基质包括脂质体，胶束，细胞膜片和光学各向同性立体脂质相基质。根据本发明的方法和组合物合成的预先折叠的合成和半合成膜多肽还允许位点特异性引入一个或多个可检测部分，例如发色团，其可以在合成期间方便地引入。本发明的方法和组合物具有多种用途。例如，它们可用于测定配体结合膜多肽和包含受体的结构域，因此对于结构/功能研究，药物筛选/选择/设计和诊断等（包括高通量应用）非常有用。本发明的方法和组合物特别适用于以前不可接近的膜多肽的FRET分析。

9. 发明申请

WO1996034878A1 SYNTHESIS OF PROTEINS BY NATIVE CHEMICAL LIGATION 审中-公开
标题翻译：通过原位化学合成蛋白质
公开(公告)号：WO1996034878A1
公开(公告)日：1996-11-07
申请号：PCT/US1995005668
申请日：1995-05-04
申请人： THE SCRIPPS RESEARCH INSTITUTE , KENT, Stephen, B., H. , MUIR, Tom, W. , DAWSON, Philip, E.
发明人： THE SCRIPPS RESEARCH INSTITUTE
IPC分类号： C07K01/02
CPC分类号： C07K1/04 , C07K1/026
摘要： Proteins of moderate size having native peptide backbones are produced by a method of native chemical ligation. Native chemical ligation employs a chemoselective reaction of two unprotected peptide segments to produce a transient thioester-linked intermediate. The transient thioester-linked intermediate then spontaneously undergoes a rearrangement to provide the full length ligation product having a native peptide bond at the ligation site. Full length ligation products are chemically identical to proteins produced by cell free synthesis. Full length ligation products may be refolded and/or oxidized, as allowed, to form native disulfide-containing protein molecules. The technique of native chemical ligation is employable for chemically synthesizing full length proteins.
摘要翻译：通过天然化学连接的方法产生具有天然肽骨架的中等体积的蛋白质。天然化学连接采用两个未保护肽段的化学选择性反应产生瞬时硫酯连接的中间体。然后瞬时硫酯连接的中间体自发地进行重排，以在连接位点提供具有天然肽键的全长连接产物。全长连接产物与通过无细胞合成产生的蛋白质化学相同。如所允许的，全长连接产物可以重折叠和/或氧化以形成天然二硫化物的蛋白质分子。天然化学连接的技术可用于化学合成全长蛋白质。

10. 发明申请

WO9911655B1 MODULAR PROTEIN LIBRARIES AND METHODS OF PREPARATION 审中-公开
标题翻译：模块蛋白图书馆和制备方法
公开(公告)号：WO9911655B1
公开(公告)日：1999-05-27
申请号：PCT/US9818096
申请日：1998-08-31
申请人： GRYPHON SCIENCES , KENT STEPHEN B H , SIANI MICHAEL A , SIMON REYNA , WILKEN JILL
发明人： KENT STEPHEN B H , SIANI MICHAEL A , SIMON REYNA , WILKEN JILL
IPC分类号： A61K38/00 , C07K1/04 , C07K14/52 , A61K38/04 , G01N33/68
CPC分类号： C07K14/523 , A61K38/00 , C07K1/04 , C07K1/047 , C07K14/522
摘要： Novel proteins and libraries comprising them are disclosed. The proteins comprise one or more functional protein modules from different parent protein molecules. The proteins and libraries are exemplified by the preparation of cross-over chemokines comprising various combinations of peptide segments derived from RANTES, SDF-1 and vMIP-I and vMIP-II. The proteins and libraries are extremely pure and can be provided in non-limiting high yields suitable for diagnostic and high-throughput screening assays.
摘要翻译：公开了包含它们的新型蛋白质和文库。蛋白质包含来自不同亲本蛋白质分子的一个或多个功能性蛋白质模块。蛋白质和文库的实例是制备包含衍生自RANTES，SDF-1和vMIP-1和vMIP-II的肽片段的各种组合的交叉趋化因子。蛋白质和文库是非常纯的，可以提供非限制性高产量，适用于诊断和高通量筛选分析。

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