公开(公告)号：WO2010011864A3

公开(公告)日：2010-04-22

申请号：PCT/US2009051585

申请日：2009-07-23

Applicant: SCRIPPS RESEARCH INST ,  REBEK JULIUS JR ,  MOISAN LIONEL ,  CARELLA ALEXANDRE ,  MANN ENRIQUE

Inventor： REBEK JULIUS JR ,  MOISAN LIONEL ,  CARELLA ALEXANDRE ,  MANN ENRIQUE

IPC: C07D403/06 ,  A61K31/50 ,  A61P15/00 ,  C07D403/02 ,  C07D403/14

CPC classification number: A61K31/501 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04 ,  C07D417/14

Abstract: The synthesis of new a-helix scaffolds mimicking i, i+3 or i+4, i+7 residues, was accomplished. The common pyridazine heterocycle originates from the easily available dimethyl pyridazine-3,6-dicarboxylate building block. These scaffolds may be thought of as synthetic counterparts of amphiphilic a-helices having a hydrophilic face along one side and a hydrophobic face along the other side of the helix.

Abstract translation: 完成了模拟i，i + 3或i + 4，i + 7残基的新α-螺旋支架的合成。 常见的哒嗪杂环来自容易获得的二甲基哒嗪-3,6-二羧酸酯结构单元。 这些支架可以被认为是具有沿着一侧具有亲水性面和沿着螺旋另一侧的疏水性面的两亲α-螺旋的合成对应物。

公开(公告)号：WO2010011325A2

公开(公告)日：2010-01-28

申请号：PCT/US2009004283

申请日：2009-07-23

Applicant: SCRIPPS RESEARCH INST ,  REBEK JULIUS ,  MANN ENRIQUE ,  MOISAN LIONEL

Inventor： REBEK JULIUS ,  MANN ENRIQUE ,  MOISAN LIONEL

IPC: C07D403/14 ,  A61K31/4439 ,  A61P29/00 ,  A61P35/00 ,  C07D401/14

CPC classification number: C07D401/14 ,  A61K31/4439 ,  A61K47/55 ,  C07D403/14

Abstract: The invention describes synthetic compounds, methods of preparation and their uses thereof an anti-inflammatory compounds that reduce inflammation associated with interleukin-1signaling.

Abstract translation: 本发明描述了合成化合物，其制备方法及其应用，其减少与白细胞介素-1信号相关的炎症的抗炎化合物。

公开(公告)号：WO2009151491A2

公开(公告)日：2009-12-17

申请号：PCT/US2009001272

申请日：2009-02-27

Applicant: SCRIPPS RESEARCH INST ,  FICHT SIMON ,  JAHNZ MICHAEL ,  GRUNEWALD JAN ,  SCHILLER STEFAN ,  SCHULTZ PETER G

Inventor： FICHT SIMON ,  JAHNZ MICHAEL ,  GRUNEWALD JAN ,  SCHILLER STEFAN ,  SCHULTZ PETER G

IPC: C12P21/02 ,  C07K14/00 ,  C12N15/63

CPC classification number: C12N15/67 ,  C12P21/02

Abstract: The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate unnatural amino acids that comprise a 1,2 aminothiol group into polypeptides. The invention provides translation systems in which polypeptides comprising unnatural amino acids that comprise a 1,2 aminothiol group can be produced. The invention also provides methods for producing polypeptides containing unnatural amino acids that comprise a 1,2 aminothiol group. Also provided by the invention are compositions comprising orthogonal aminoacyl-tRNA synthetases that preferentially aminoacylate a cognate orthogonal tRNA with unnatural amino acids that comprise a 1,2 aminothiol group. The invention provides methods for the synthesis of the unnatural amino acid 2-amino-3 -(4-(2-amino-3 -mercaptopropan-amido)phenyl)-propanoic acid.

Abstract translation: 本发明涉及tRNA和氨酰-tRNA合成酶的正交对，其可将含有1,2氨基硫醇基团的非天然氨基酸掺入多肽中。 本发明提供翻译系统，其中可以制备包含含有1,2氨基硫醇基团的非天然氨基酸的多肽。 本发明还提供了生产含有包含1,2氨基硫醇基团的非天然氨基酸的多肽的方法。 本发明还提供了包含正交氨酰-tRNA合成酶的组合物，其优先地将同源正交tRNA与包含1,2-氨基硫醇基团的非天然氨基酸氨酰化。 本发明提供了合成非天然氨基酸2-氨基-3-（4-（2-氨基-3-巯基丙酰胺基）苯基） - 丙酸的方法。

公开(公告)号：WO2009099672A3

公开(公告)日：2009-11-12

申请号：PCT/US2009000813

申请日：2009-02-07

Applicant: SCRIPPS RESEARCH INST ,  GRUNEWALD JAN ,  TSAO MENG-LIN ,  PERERA ROSHAN ,  LERNER RICHARD A ,  SMIDER VAUGHN V ,  SCHULTZ PETER G

Inventor： GRUNEWALD JAN ,  TSAO MENG-LIN ,  PERERA ROSHAN ,  LERNER RICHARD A ,  SMIDER VAUGHN V ,  SCHULTZ PETER G

IPC: A61K39/395 ,  A61K31/198 ,  A61P25/28 ,  A61P35/00 ,  A61P37/04 ,  C12P21/02 ,  C12Q1/68

CPC classification number: C07K16/241 ,  A61K31/19 ,  A61K39/0008 ,  C07K16/44

Abstract: The present invention comprises methods and compositions for producing and/or enhancing an immunological response in a subject against a target moiety such as a disease-related moiety by administration of an antigenic version of the target moiety having one or more unnatural amino acid and/or by administration of an antibody against a version of a target moiety having one or more unnatural amino acid which antibody is cross reactive with the natural target moiety.

Abstract translation: 本发明包括用于通过施用具有一个或多个非天然氨基酸的靶部分的抗原性版本来产生和/或增强受试者中针对靶部分例如疾病相关部分的免疫应答的方法和组合物，和/或 通过施用针对具有一个或多个非天然氨基酸的靶部分版本的抗体，该抗体与天然靶标部分交叉反应。

公开(公告)号：WO2009075847A3

公开(公告)日：2009-09-11

申请号：PCT/US2008013568

申请日：2008-12-10

Applicant: SCRIPPS RESEARCH INST ,  YOUNG TRAVIS ,  SCHULTZ PETER G

Inventor： YOUNG TRAVIS ,  SCHULTZ PETER G

IPC: C12N1/19

CPC classification number: C12N15/815 ,  C07K2319/00 ,  C07K2319/55 ,  C12N9/93 ,  C12P21/02

Abstract: The invention provides orthogonal translation systems for the production of polypeptides comprising unnatural amino acids in methylotrophic yeast such as Pichia pastoris. Methods for producing polypeptides comprising unnatural amino acids in methylotrophic yeast such as Pichia pastoris are also provided.

Abstract translation: 本发明提供了用于在甲基营养酵母如巴斯德毕赤酵母中产生包含非天然氨基酸的多肽的正交翻译系统。 还提供了在甲基营养酵母如巴斯德毕赤酵母中产生包含非天然氨基酸的多肽的方法。

公开(公告)号：WO2009061369A3

公开(公告)日：2009-09-03

申请号：PCT/US2008012363

申请日：2008-10-31

Applicant: SCRIPPS RESEARCH INST ,  LIU CHANG ,  TSAO MENG-LIN ,  SMIDER VAUGHN ,  SCHULTZ PETER G

Inventor： LIU CHANG ,  TSAO MENG-LIN ,  SMIDER VAUGHN ,  SCHULTZ PETER G

IPC: C12N15/10 ,  C12N15/09 ,  C12N15/12 ,  C12Q1/68 ,  G01N33/68

CPC classification number: C12N15/1037 ,  C12N15/1058 ,  C12N15/67 ,  C40B40/08 ,  C40B40/10

Abstract: The invention provides methods and compositions for screening polypeptide libraries that include variants comprising unnatural amino acids. In addition, the invention provides vector packaging systems and methods for packaging a nucleic acid in a vector. Compositions of vectors produced by the methods and systems are also provided

Abstract translation: 本发明提供了用于筛选多肽文库的方法和组合物，其包括包含非天然氨基酸的变体。 此外，本发明提供了用于在载体中包装核酸的载体包装系统和方法。 还提供了由方法和系统生成的载体的组合物

公开(公告)号：WO2007082296A8

公开(公告)日：2009-07-30

申请号：PCT/US2007060480

申请日：2007-01-12

Applicant: SCRIPPS RESEARCH INST ,  KUHN PETER ,  KOLAKTRA ANAND ,  BROOUN ALEXEI ,  CHRENCIK JILL ,  KRAUS MICHELLE

Inventor： KUHN PETER ,  KOLAKTRA ANAND ,  BROOUN ALEXEI ,  CHRENCIK JILL ,  KRAUS MICHELLE

IPC: G06G7/48

CPC classification number: G06F19/706 ,  G06F19/16

Abstract: The invention relates to the three-dimensional structure of a crystal of an EphB4 receptor complexed with a ligand. The three-dimensional structure of a Receptor-Ligand Complex is disclosed. The receptor-ligand crystal structure, wherein the ligand is an inhibitor molecule, is useful for providing structural information that may be integrated into drug screening and drug design processes. Thus, the invention also relates to methods for utilizing the crystal structure of the Receptor-Ligand Complex for identifying, designing, selecting, or testing inhibitors of the EphB4 receptor protein, such inhibitors being useful as therapeutics for the treatment or modulation of i) diseases; ii) disease symptoms; or iii) the effect of other physiological events mediated by the receptor.

Abstract translation: 本发明涉及与配体络合的EphB4受体的晶体的三维结构。 公开了受体配体复合物的三维结构。 受体 - 配体晶体结构，其中配体是抑制剂分子，可用于提供可被整合到药物筛选和药物设计过程中的结构信息。 因此，本发明还涉及利用受体配体复合物的晶体结构鉴定，设计，选择或测试EphB4受体蛋白质的抑制剂的方法，所述抑制剂可用作治疗或调节i）疾病 ; ii）疾病症状; 或iii）由受体介导的其它生理事件的作用。

公开(公告)号：WO2007021342A3

公开(公告)日：2009-05-28

申请号：PCT/US2006018910

申请日：2006-05-12

Applicant: SCRIPPS RESEARCH INST ,  CHANG GEOFFREY ,  REYES CHRISTOPHER L ,  WARD ANDREW ,  YU JODIE

Inventor： CHANG GEOFFREY ,  REYES CHRISTOPHER L ,  WARD ANDREW ,  YU JODIE

IPC: G01N33/49 ,  C12Q1/00 ,  G06F19/16

CPC classification number: G01N33/6872 ,  C07K14/705 ,  C07K16/1235 ,  C07K2299/00 ,  G01N2333/705 ,  G06F19/16 ,  G06F19/701 ,  G06F19/706 ,  Y02A90/22 ,  Y02A90/26

Abstract: The invention relates to the three-dimensional structure of a crystal of a transporter protein complexed with a ligand. The three-dimensional structure of the transporter-ligand complex is disclosed. The transporter-ligand crystal structure, wherein the ligand is an inhibitor molecule, is useful for providing structural information that may be integrated into drug screening and drug design processes. Thus, the invention also relates to methods for utilizing the crystal structure of the transporter-ligand complex for identifying, designing, selecting, or testing inhibitors of the transporter protein, such inhibitors being useful as therapeutics for the treatment or modulation of i) diseases; ii) disease symptoms; or iii) the effect of other physiological events mediated by the transporter.

Abstract translation: 本发明涉及与配体络合的转运蛋白的晶体的三维结构。 公开了转运体 - 配体复合物的三维结构。 其中配体是抑制剂分子的转运体 - 配体晶体结构可用于提供可以整合到药物筛选和药物设计过程中的结构信息。 因此，本发明还涉及利用转运体 - 配体复合物的晶体结构鉴定，设计，选择或测试转运蛋白抑制剂的方法，所述抑制剂可用作治疗或调节i）疾病的治疗剂; ii）疾病症状; 或iii）由转运蛋白介导的其他生理事件的影响。

公开(公告)号：WO2008133759A3

公开(公告)日：2009-05-14

申请号：PCT/US2008000452

申请日：2008-01-10

Applicant: SCRIPPS RESEARCH INST ,  CHISARI FRANCIS V

Inventor： CHISARI FRANCIS V

IPC: A61K38/00

CPC classification number: C07K14/005 ,  A61K38/00 ,  C12N2770/24122 ,  C12N2770/24222

Abstract: The present application is directed to antiviral peptides, methods of using these peptides to prevent or inhibit infections by a human immunodeficiency virus or a virus from the Flaviviridae family, and pharmaceutical compositions and combinations, as well as articles of manufacture comprising these peptides.

Abstract translation: 本申请涉及抗病毒肽，使用这些肽预防或抑制人类免疫缺陷病毒或来自黄病毒科的病毒感染的方法，以及药物组合物和组合以及包含这些肽的制品。

公开(公告)号：WO2008055145A3

公开(公告)日：2009-04-09

申请号：PCT/US2007082980

申请日：2007-10-30

Applicant: SCRIPPS RESEARCH INST ,  GRIFFIN JOHN H ,  MOSNIER LAURENT O ,  GALE ANDREW J

Inventor： GRIFFIN JOHN H ,  MOSNIER LAURENT O ,  GALE ANDREW J

IPC: A61K38/17 ,  A61K38/36 ,  C12N9/50

CPC classification number: A61K38/4866 ,  C12N9/6464 ,  C12Y304/21069

Abstract: Variants (mutants) of recombinant activated protein C (APC) or recombinant protein C (prodrug, capable of being converted to APC) that have substantial reductions in anticoagulant activity but that retain normal levels of anti-apoptotic activity are provided. Three examples of such recombinant APC mutants are KKK191-193AAA-APC, RR229/230AA-APC, and RR229/230AA plus KKK191-193AAA-APC. APC variants and prodrugs of the invention have the desirable property of being cytoprotective (anti-apoptotic effects), while having significantly reduced risk of bleeding. The invention also provides a method of using the APC variants or prodrugs of the invention to treat subjects who will benefit from APC's cytoprotective activities that are independent of APC's anticoagulant activity. These subjects include patients at risk of damage to blood vessels or tissue in various organs caused, at least in part, by apoptosis. At risk patients include, for example, those suffering (severe) sepsis, ischemia/reperfusion injury, ischemic stroke, acute myocardial infarction, acute or chronic neurodegenerative diseases, or those undergoing organ transplantation or chemotherapy, among other conditions. Methods of screening for variants of recombinant protein C or APC that are useful in accordance with the invention are also provided.

Abstract translation: 提供重组活化蛋白C（APC）或重组蛋白C（前体药物，能够转化为APC）的变体（突变体），其具有显着降低抗凝活性，但保持正常水平的抗凋亡活性。 这些重组APC突变体的三个实例是KKK191-193AAA-APC，RR229 / 230AA-APC和RR229 / 230AA加上KKK191-193AAA-APC。 本发明的APC变体和前药具有细胞保护性（抗凋亡作用）的期望性质，同时具有显着降低的出血风险。 本发明还提供了使用本发明的APC变体或前药来治疗受益于APC的细胞保护活性而不受APC抗凝活性影响的受试者的方法。 这些受试者包括至少部分地通过细胞凋亡而导致各种器官的血管损伤或组织损伤风险的患者。 在危险中，患者包括例如患有（严重）败血症，缺血/再灌注损伤，缺血性卒中，急性心肌梗死，急性或慢性神经变性疾病或经历器官移植或化疗的患者等。 还提供了筛选根据本发明有用的重组蛋白C或APC的变体的方法。