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1. 发明申请

US20110296539A1 Mutant Alpha-Synuclein, and Methods Using Same 有权
标题翻译：突变型α-突触核蛋白，和使用相同的方法
公开(公告)号：US20110296539A1
公开(公告)日：2011-12-01
申请号：US13057680
申请日：2009-08-07
申请人： Markus Zweckstetter , Pinar Karpinar , Christian Griesinger
发明人： Markus Zweckstetter , Pinar Karpinar , Christian Griesinger
IPC分类号： G01N33/00 , C12N15/79 , C12N1/19 , A01K67/027 , C12Q1/02 , C07K14/435 , A01K67/033 , C12N15/12 , C12N5/10
CPC分类号： A01K67/0275 , A01K67/0336 , A01K67/0339 , A01K2227/105 , A01K2227/106 , A01K2227/703 , A01K2227/706 , A01K2267/03 , C07K14/47 , C12N15/102
摘要： The present invention relates to a mutant human alpha-synuclein with increased toxicity compared to wild-type alpha-synuclein, or a homologue thereof, wherein the mutant alpha-synuclein or homologue thereof comprises at least one amino acid substitution selected from the group consisting of a substitution at the alanine at position 56 (A56), at the alanine at position 76 (A76), at the methionine at position 127 (M127) and/or at the valine at position 118 (V118), as defined in the claims. Further, the invention relates to a polynucleotide encoding the mutant alpha-synuclein or homologue thereof, or an expression vector comprising said polynucleotide, a cell comprising the polynucleotide or expression vector, as defined in the claims. Also, a non-human animal comprising the cell of the invention is provided, as defined in the claims. Finally, the invention provides methods for identifying a substance that prevents or reduces toxicity of alpha-synuclein, as defined in the claims.
摘要翻译：本发明涉及与野生型α-突触核蛋白或其同源物相比具有增加的毒性的突变型人α-突触核蛋白，其中所述突变型α-突触核蛋白或其同源物包含至少一种选自以下的氨基酸取代：如在权利要求中定义的在位置56（A56）的丙氨酸，位置76（A76）的丙氨酸，位置127的甲硫氨酸（M127）和/或缬氨酸位置118（V118）处的取代。此外，本发明涉及编码突变型α-突触核蛋白或其同系物的多核苷酸，或包含所述多核苷酸的表达载体，包含如权利要求中所定义的多核苷酸或表达载体的细胞。而且，如权利要求中所定义的，提供包含本发明的细胞的非人动物。最后，本发明提供了鉴定如权利要求中所定义的预防或减少α-突触核蛋白毒性的物质的方法。

2. 发明授权

US08809505B2 Mutant alpha-synuclein, and methods using same 有权
标题翻译：突变型α-突触核蛋白，以及使用其的方法
公开(公告)号：US08809505B2
公开(公告)日：2014-08-19
申请号：US13057680
申请日：2009-08-07
申请人： Markus Zweckstetter , Pinar Karpinar , Christian Griesinger
发明人： Markus Zweckstetter , Pinar Karpinar , Christian Griesinger
IPC分类号： C12N15/12 , A61K38/00
CPC分类号： A01K67/0275 , A01K67/0336 , A01K67/0339 , A01K2227/105 , A01K2227/106 , A01K2227/703 , A01K2227/706 , A01K2267/03 , C07K14/47 , C12N15/102
摘要： The present invention relates to a mutant human alpha-synuclein with increased toxicity compared to wild-type alpha-synuclein, or a homologue thereof, wherein the mutant alpha-synuclein or homologue thereof comprises at least one amino acid substitution selected from the group consisting of a substitution at the alanine at position 56 (A56), at the alanine at position 76 (A76), at the methionine at position 127 (M127) and/or at the valine at position 118 (V118), as defined in the claims. Further, the invention relates to a polynucleotide encoding the mutant alpha-synuclein or homologue thereof, or an expression vector comprising said polynucleotide, a cell comprising the polynucleotide or expression vector, as defined in the claims. Also, a non-human animal comprising the cell of the invention is provided, as defined in the claims. Finally, the invention provides methods for identifying a substance that prevents or reduces toxicity of alpha-synuclein, as defined in the claims.
摘要翻译：本发明涉及与野生型α-突触核蛋白或其同源物相比具有增加的毒性的突变型人α-突触核蛋白，其中所述突变型α-突触核蛋白或其同源物包含至少一种选自以下的氨基酸取代：如在权利要求中定义的在位置56（A56）的丙氨酸，位置76（A76）的丙氨酸，位置127的甲硫氨酸（M127）和/或缬氨酸位置118（V118）处的取代。此外，本发明涉及编码突变型α-突触核蛋白或其同系物的多核苷酸，或包含所述多核苷酸的表达载体，包含如权利要求中所定义的多核苷酸或表达载体的细胞。而且，如权利要求中所定义的，提供包含本发明的细胞的非人动物。最后，本发明提供了鉴定如权利要求中所定义的预防或减少α-突触核蛋白毒性的物质的方法。

3. 发明授权

US5939527A Tetrapeptides as antitumor agents 失效
标题翻译：四肽作为抗肿瘤剂
公开(公告)号：US5939527A
公开(公告)日：1999-08-17
申请号：US688335
申请日：1996-07-30
申请人： Teresa Barlozzari , Andreas Haupt , Bernd Janssen , Christian Griesinger , Daniel Belik , Michael Boretzky
发明人： Teresa Barlozzari , Andreas Haupt , Bernd Janssen , Christian Griesinger , Daniel Belik , Michael Boretzky
IPC分类号： A61K38/00 , A61P35/00 , C07K4/00 , C07K5/02 , C07K5/00
CPC分类号： C07K5/0205 , A61K38/00
摘要： The present invention provides anti-tumor peptides of Formula I,A--B--NR.sup.3 --CHD--CH(OCH.sub.3)--CH.sub.2 CO--E--K (I),and the acid salts thereof. A is an amino acid residue selected from the group consisting of N-methyl-D-prolyl, N-methyl-D-homoprolyl and N,N-dimethyl-2-ethylphenylglycyl, or an amino acid residue of the formula R.sup.1 R.sup.2 N--CHX--CO, wherein R.sup.1 is a-methyl group or an ethyl group, R.sup.2 is a hydrogen atom, a methyl group or an ethyl group, and X is an alkyl group. B is an amino acid residue selected from the group consisting of valyl, isoleucyl, leucyl, and 2-t-butylglycyl. R.sup.3 is a hydrogen atom or a methyl group. D is a normal or branched C.sub.2 -C.sub.5 -alkyl group. E is an amino acid residue selected from the group consisting of prolyl, homoprolyl, 5-methylprolyl, and phenylalanyl, or E is a residue derived from an amino acid comprising a pyrrolidine group. K is an alkoxy group or an amino group.An additional embodiment of the present invention is a method for treating a malignancy in a mammal, such as a human, comprising administering to the mammal an effective amount of a compound or compounds of Formula I in a pharmaceutically acceptable composition.
摘要翻译：本发明提供式I，A-B-NR3-CHD-CH（OCH3）-CH2CO-E-K（I）的抗肿瘤肽及其酸式盐。 A是选自N-甲基-D-脯氨酰基，N-甲基-D-正戊基和N，N-二甲基-2-乙基苯基甘氨酰或式R 1 R 2 N-CHX-的氨基酸残基的氨基酸残基， CO，其中R1是α-甲基或乙基，R2是氢原子，甲基或乙基，X是烷基。 B是选自缬氨酰基，异亮氨酰基，亮氨酰基和2-叔丁基甘氨酰基的氨基酸残基。 R3是氢原子或甲基。 D是正链或支链C 2 -C 5 - 烷基。 E是选自脯氨酰基，同环戊基，5-甲基脯氨酰基和苯丙氨酰基的氨基酸残基，或E是衍生自包含吡咯烷基的氨基酸的残基。 K是烷氧基或氨基。本发明的另一个实施方案是用于治疗哺乳动物（例如人）的恶性肿瘤的方法，包括向所述哺乳动物施用有效量的药学上可接受的组合物中的式I化合物或化合物。

4. 发明授权

US5741892A Pentapeptides as antitumor agents 失效
标题翻译：五肽作为抗肿瘤剂
公开(公告)号：US5741892A
公开(公告)日：1998-04-21
申请号：US688334
申请日：1996-07-30
申请人： Teresa Barlozzari , Andreas Haupt , Bernd Janssen , Christian Griesinger , Daniel Belik , Michael Boretzky , George R. Pettit
发明人： Teresa Barlozzari , Andreas Haupt , Bernd Janssen , Christian Griesinger , Daniel Belik , Michael Boretzky , George R. Pettit
IPC分类号： A61K38/00 , A61P1/00 , A61P11/00 , A61P15/00 , A61P35/00 , C07K7/02 , C07K7/00
CPC分类号： C07K7/02 , A61K38/00
摘要： The present invention provides anti-tumor peptides of Formula I, A-B-N (CH.sub.3)-CHD-CH(OCH.sub.3)-CH.sub.2 CO-Pro-Pro-K (I), and the acid salts thereof. A is an amino acid residue of the formula (CH.sub.3).sub.2 N--CHX--CO, wherein X is a normal or branched alkyl group. B is an amino acid residue selected from the group consisting of valyl, isoleucyl, leucyl, and 2-t-butylglycyl. D is a normal or branched C.sub.3 -C.sub.4 -alkyl group. K is a t-butoxy group or a substituted amino group. An additional embodiment of the present invention is a method for treating a malignancy in a mammal, such as a human, comprising administering to the mammal an effective amount of a compound or compounds of Formula I in a pharmaceutically acceptable composition.
摘要翻译：本发明提供式I，A-B-N（CH 3）-CHD-CH（OCH 3）-CH 2 CO-Pro-Pro-K（I）的抗肿瘤肽及其酸式盐。 A是式（CH 3）2 N-CHX-CO的氨基酸残基，其中X是正或支链烷基。 B是选自缬氨酰基，异亮氨酰基，亮氨酰基和2-叔丁基甘氨酰基的氨基酸残基。 D是正链或支链C 3 -C 4 - 烷基。 K为叔丁氧基或取代氨基。本发明的另一个实施方案是用于治疗哺乳动物（例如人）的恶性肿瘤的方法，包括向所述哺乳动物施用有效量的药学上可接受的组合物中的式I化合物或化合物。

5. 发明申请

US20110293520A1 NEW DRUG FOR INHIBITING AGGREGATION OF PROTEINS INVOLVED IN DISEASES LINKED TO PROTEIN AGGREGATION AND/OR NEURODEGENERATIVE DISEASES 审中-公开
标题翻译：用于抑制与蛋白质聚集和/或神经干细胞病变相关的疾病相关蛋白聚集的新药
公开(公告)号：US20110293520A1
公开(公告)日：2011-12-01
申请号：US12996833
申请日：2009-06-09
申请人： Armin Giese , Uwe Bertsch , Hans Kretzschmar , Mathias Habeck , Thomas Hirschberger , Paul Tavan , Christian Griesinger , Andrei Leonov , Sergey Ryazanov , Petra Weber , Markus Geissen , Martin H. Groschup , Jens Wagner
发明人： Armin Giese , Uwe Bertsch , Hans Kretzschmar , Mathias Habeck , Thomas Hirschberger , Paul Tavan , Christian Griesinger , Andrei Leonov , Sergey Ryazanov , Petra Weber , Markus Geissen , Martin H. Groschup , Jens Wagner
IPC分类号： A61K51/04 , C07D261/08 , C07D231/12 , C07D233/64 , C07D271/06 , A61K31/4155 , A61K31/42 , A61K31/415 , A61K31/4164 , A61K31/4245 , A61K49/00 , A61P25/16 , A61P25/00 , A61P25/28 , G01N33/566 , C07D405/10
CPC分类号： C07D231/12 , A61K31/40 , A61K31/415 , A61K31/4155 , A61K31/4164 , A61K31/42 , A61K31/4245 , C07D207/333 , C07D231/06 , C07D233/64 , C07D261/08 , C07D271/06 , C07D405/04 , C07D413/04 , G01N33/6896 , G01N2800/2828
摘要： The present invention relates to a compound represented by formula (E). The present invention also relates to a compound represented by the formula (E) for use in the treatment or prevention of diseases linked to protein aggregation and/or neurodegenerative diseases. Moreover, the present invention relates to pharmaceutical and diagnostic compositions comprising the compound of the invention as well as to a kit. Furthermore, the present invention relates to a method of imaging deposits of aggregated protein. A kit for preparing a detectably labelled compound of the present invention is also disclosed. Formula (E) wherein X, Y and L are independently nondirectionally selected from —C(R1)(R2)—, —C(R3)═, —N(R4)—, —N═, —N+(R5)═, —O— and —S—; M and Z are independently nondirectionally selected from formula (I) and formula (II).
摘要翻译：本发明涉及由式（E）表示的化合物。本发明还涉及用于治疗或预防与蛋白质聚集和/或神经变性疾病相关的疾病的由式（E）表示的化合物。此外，本发明涉及包含本发明化合物以及试剂盒的药物和诊断组合物。此外，本发明涉及一种成像聚集蛋白沉积物的方法。还公开了用于制备本发明的可检测标记的化合物的试剂盒。式（E）其中X，Y和L分别独立地选自-C（R 1）（R 2） - ， - C（R 3）=，-N（R 4） - ， - N =，-N +（R 5） -O-和-S-; M和Z独立地选自式（I）和式（II）。

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