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1. 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。

2. 发明申请

WO1998028434A1 GENERAL CHEMICAL LIGATION 审中-公开
标题翻译：一般化学物质
公开(公告)号：WO1998028434A1
公开(公告)日：1998-07-02
申请号：PCT/US1996020610
申请日：1996-12-24
申请人： THE SCRIPPS RESEARCH INSTITUTE , KENT, Stephen, B., H. , MUIR, Tom, W. , DAWSON, Philip, E. , BARK, Steven, J. , CANNE, Lynne
发明人： THE SCRIPPS RESEARCH INSTITUTE
IPC分类号： C12P21/00
CPC分类号： C07K1/023 , C07K1/026 , C07K1/04 , C07K1/10 , C07K1/1075
摘要： Oligopeptides are ligated to form ligation peptide products. In the first step, two starting oligopeptides are ligated to form an intermediate having an aminothioester linkage. In the second step, the aminothioester linkage undergoes a rearrangement to form a peptide having an N-substituted amide linkage. In an optional third step, the N-substitution of the amide linkage is chemically removed to form a native peptide linkage.
摘要翻译：连接寡肽以形成连接肽产物。在第一步中，将两个起始的寡肽连接以形成具有氨基硫酯键的中间体。在第二步中，氨基酯连接经历重排以形成具有N-取代的酰胺键的肽。在任选的第三步中，酰胺键的N-取代被化学去除以形成天然肽键。

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

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。

5. 发明申请

WO1998035927A1 PEG-BOUND ALKALOID LIGANDS AND USE THEREOF 审中-公开
标题翻译： PEG环糊精配体及其用途
公开(公告)号：WO1998035927A1
公开(公告)日：1998-08-20
申请号：PCT/US1997002442
申请日：1997-02-14
申请人： THE SCRIPPS RESEARCH INSTITUTE , JANDA, Kim, D. , HAN, Hyunsoo
发明人： THE SCRIPPS RESEARCH INSTITUTE
IPC分类号： C07C29/03
CPC分类号： C07C29/48 , C07C33/26 , C07C31/20
摘要： Polyethylene glycol monomethyl ether-bound alkaloid ligands (PEG-bound alkaloid ligands) are constructed and employed in the ligand-accelerated catalytic (LAC) Sharpless asymmetric dihydroxylation reaction (AD) with a range of olefins. The PEG serves as a scaffold which allows simple product separation, polymer-bound ligand recovery, and recycling of the chiral liquid phase support without a loss of catalytic activity or ligand acceleration.
摘要翻译：聚乙二醇单甲醚结合的生物碱配体（PEG结合的生物碱配体）被构建并用于具有一系列烯烃的配体加速催化（LAC）Sharpless不对称二羟基化反应（AD）中。 PEG用作支架，其允许简单的产物分离，聚合物结合的配体回收和手性液相支持物的循环，而不会失去催化活性或配体加速。

6. 发明申请

WO1998025929A1 EPOTHILONE ANALOGS 审中-公开
标题翻译： EPOTHILONE模拟
公开(公告)号：WO1998025929A1
公开(公告)日：1998-06-18
申请号：PCT/EP1997007011
申请日：1997-12-12
申请人： NOVARTIS AG , THE SCRIPPS RESEARCH INSTITUTE , NICOLAOU, Costa, Kyriacos , HE, Yun , NINKOVIC, Sacha , PASTOR, Joaquin , ROSCHANGAR, Frank , SARABIA, Francisco , VALLBERG, Hans , VOURLOUMIS, Dionisios , WINSSINGER, Nicolas , YANG, Zhen , KING, Nigel, Paul , FINLAY, Maurice, Raymond, Verschoyle
发明人： NOVARTIS AG , THE SCRIPPS RESEARCH INSTITUTE
IPC分类号： C07D493/04
CPC分类号： C07D417/06 , C07D313/00 , C07D493/04
摘要： Epothilone A, epothilone B, analogs of epothilone and libraries of epothilone analogs are synthesized. Epothilone A and B are known anticancers agents that derive their anticancer activity by the prevention of mitosis through the induction and stabilization of microtubulin assembly. The analogs of epothilone are novel. Several of the analogs are demonstrated to have a superior cytotoxic activity as compared to epothilone A or epothilone B as demonstrated by their enhanced ability to induce the polymerization and stabilization of microtubules.
摘要翻译：埃博霉素A，埃坡霉素B，埃坡霉素类似物和埃坡霉素类似物文库合成。埃博霉素A和B是已知的抗癌剂，其通过微管蛋白装配的诱导和稳定来预防有丝分裂来获得它们的抗癌活性。埃坡霉素的类似物是新颖的。与埃坡霉素A或埃坡霉素B相比，几种类似物被证明具有优异的细胞毒性活性，如通过增强诱导微管聚合和稳定化的能力所证实的。

7. 发明申请

WO1998008854A2 ORGANIC COMPOUNDS 审中-公开
标题翻译：有机化合物
公开(公告)号：WO1998008854A2
公开(公告)日：1998-03-05
申请号：PCT/EP1997004649
申请日：1997-08-26
申请人： NOVARTIS AG , THE SCRIPPS RESEARCH INSTITUTE , WONG, Chi-Huey , LIN, Chun-Cheng , WOLTERING, Thomas, J. , MARRON, Thomas, G. , MORIS-VARAS, Francisco , JABLONOWSKI, Jill , WEITZ-SCHMIDT, Gabriele
发明人： NOVARTIS AG , THE SCRIPPS RESEARCH INSTITUTE
IPC分类号： C07H15/00
CPC分类号： C07H7/02 , C07H15/00
摘要： Sialyl Lewis X mimetics which mimic the inhibition of selectin-mediated cellular adhesion by sialyl Lewis X having a core of formula (I).
摘要翻译：本发明涉及模拟选择素诱导的细胞粘附的路易斯X唾液酸化抑制的路易斯X唾液酸模拟物，其具有式（I）的核心。

8. 发明申请

WO1997048819A1 CASSAVA VEIN MOSAIC VIRUS PROMOTERS AND USES THEREOF 审中-公开
标题翻译： CASSAVA VEIN MOSAIC VIRUS促销者及其用途
公开(公告)号：WO1997048819A1
公开(公告)日：1997-12-24
申请号：PCT/US1997010376
申请日：1997-06-20
申请人： THE SCRIPPS RESEARCH INSTITUTE , VERDAGUER, Bertrand , DE KOCHKO, Alexandre , BEACHY, Roger, N. , FAUQUET, Claude
发明人： THE SCRIPPS RESEARCH INSTITUTE
IPC分类号： C12P21/06
CPC分类号： C07K14/005 , C12N15/8216 , C12N2730/00022
摘要： The invention relates to compositions and methods useful for the production of transgenic plants. In particular, the invention relates to cassava vein mosaic virus (CsVMV) promoter sequences and expression cassettes containing CsVMV promoter sequences. The invention describes nucleic acid molecules, vectors and transgenic plants containing promoters derived from CsVMV promoter that are operatively linked to heterologous DNA sequences, and methods for producing transgenic plants containing these promoters.
摘要翻译：本发明涉及可用于生产转基因植物的组合物和方法。特别地，本发明涉及木薯静脉花叶病毒（CsVMV）启动子序列和含有CsVMV启动子序列的表达盒。本发明描述了含有源自与异源DNA序列有效连接的CsVMV启动子的启动子的核酸分子，载体和转基因植物以及用于产生含有这些启动子的转基因植物的方法。

9. 发明申请

WO1997041526A1 SMALL MOLECULE MIMETICS OF ERYTHROPOIETIN 审中-公开
标题翻译： ERYTHROPOIETIN的小分子物质
公开(公告)号：WO1997041526A1
公开(公告)日：1997-11-06
申请号：PCT/US1997007218
申请日：1997-04-28
申请人： THE SCRIPPS RESEARCH INSTITUTE
发明人： THE SCRIPPS RESEARCH INSTITUTE , WILSON, Ian, A. , LIVNAH, Oded , STURA, Enrico, A. , JOHNSON, Dana, L. , JOLLIFFE, Linda, K.
IPC分类号： C07B61/00 , A61B5/00 , C07K7/08 , C07K14/00 , C07K14/505 , G01N33/74 , G06Q50/22
CPC分类号： G01N33/746 , C07K7/08 , C07K14/001 , C07K14/505 , Y10S707/99943
摘要： The invention features computer-assisted methods (100, 102, 104, 106, 200, 202, 204) for identifying molecules which will bind to the EPO receptor and act as an erythropoietin (EPO) mimetic. Preferred EPO mimetics identified using the method of the invention act as agonists of the EPO receptor in one or more in vitro or in vivo biological assays of EPO activity.
摘要翻译：本发明的特征在于用于鉴定将结合EPO受体并用作促红细胞生成素（EPO）模拟物的分子的计算机辅助方法（100,102,104,106,200,2002,204）。使用本发明的方法鉴定的优选EPO模拟物在EPO活性的一个或多个体外或体内生物测定中作为EPO受体的激动剂。

10. 发明申请

WO1997021100A1 HIV PROTEASE INHIBITORS 审中-公开
标题翻译：艾滋病病毒蛋白酶抑制剂
公开(公告)号：WO1997021100A1
公开(公告)日：1997-06-12
申请号：PCT/US1996019571
申请日：1996-12-09
申请人： THE SCRIPPS RESEARCH INSTITUTE , WONG, Chi-Huey , SLEE, Deborah, H. , LASLO, Karen
发明人： THE SCRIPPS RESEARCH INSTITUTE
IPC分类号： G01N33/53
CPC分类号： C12Q1/37 , C07D207/08 , C07D207/12 , C07D207/16 , C07D211/60 , C12Q1/18 , C40B40/04 , G01N2333/16
摘要： Combinatorial libraries of HIV and FIV protease inhibitors are characterized by alpha -keto amide or hydroxyethylamine core structures flanked by on one side by substituted pyrrolidines, piperidines, or azasugars and on the other side by phenylalanine, tyrosine, or substituted tyrosines. The libraries are synthesized via a one step coupling reaction. Highly efficacious drug candidates are identified by screening the libraries for binding and inhibitory activity against both HIV and FIV protease. Drug candidates displaying clinically useful activity against both HIV and FIV protease are identified as being potentially resistive against a loss of inhibitory activity due to development of resistant strains of HIV.
摘要翻译：艾滋病毒和FIV蛋白酶抑制剂的组合文库的特征在于α-酮酰胺或羟乙基胺核心结构，其侧面为取代的吡咯烷酮，哌啶或氮杂异构体，另一侧为苯丙氨酸，酪氨酸或取代的酪氨酸。文库通过一步偶联反应合成。通过筛选文库对HIV和FIV蛋白酶的结合和抑制活性来鉴定高效药物候选物。鉴于HIV和FIV蛋白酶对临床有用的活性的候选药物被鉴定为可能阻止由于HIV的抗性株的发展而导致的抑制活性丧失。

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