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1. 发明授权

US06169074A Peptide inhibitors of neurotransmitter secretion by neuronal cells 失效
标题翻译：神经递质分泌神经元细胞的肽抑制剂
公开(公告)号：US06169074A
公开(公告)日：2001-01-02
申请号：US08819286
申请日：1997-03-18
申请人： Mauricio Montal , Jaume M. Canaves , Antonio V. Ferrer-Monteil
发明人： Mauricio Montal , Jaume M. Canaves , Antonio V. Ferrer-Monteil
IPC分类号： C07K708
CPC分类号： C07K14/33 , A61K38/00 , C07K2319/00 , Y02A50/469
摘要： The invention consists of peptides which inhibit the secretion of neurotransmitters from synaptic vesicles. The peptides of the invention are believed to mimic the activity of neurotoxins produced by Clostridium botulinum and tetani (including botulinum serotypes A, B, C, D, E, F and G). Structurally, the peptides are comprised of amino acid fragments from the substrate binding domains selected from three proteins which bind to form a receptor for docking of synaptic vesicles to the plasma membranes of neuronal cells; i.e., SNAP-25, VAMP-2 and syntaxin. Certain of the inventive peptides exhibit strong inhibitory activity; e.g., 50% or greater decline in neurotransmitter release is obtained at even nanomolar concentrations. The peptides are suited for use as substitutes for Clostridium neurotoxins in clinical applications and in compounds for targeted delivery of drugs into neural cells.
摘要翻译：本发明由抑制神经递质从突触小泡分泌的肽组成。据信本发明的肽模拟肉毒杆菌和破伤风（包括肉毒杆菌血清型A，B，C，D，E，F和G）产生的神经毒素的活性。结构上，肽由选自三种蛋白质的底物结合结构域的氨基酸片段组成，三种蛋白质结合形成突触小泡对接神经元细胞的质膜的受体; 即SNAP-25，VAMP-2和syntaxin。某些本发明的肽表现出强的抑制活性; 例如在甚至纳摩尔浓度下获得神经递质释放的50％或更大的下降。这些肽适合用作临床应用中的Clostridium神经毒素的替代物和用于将药物靶向递送至神经细胞的化合物。

2. 发明授权

US07022882B2 NMDA receptor channel blocker with neuroprotective activity 失效
标题翻译：具有神经保护活性的NMDA受体通道阻滞剂
公开(公告)号：US07022882B2
公开(公告)日：2006-04-04
申请号：US10381956
申请日：2001-10-05
申请人： Kwok-Keung Tai , Sylvie E. Blondelle , Richard A. Houghten , Mauricio Montal
发明人： Kwok-Keung Tai , Sylvie E. Blondelle , Richard A. Houghten , Mauricio Montal
IPC分类号： C07C211/13 , C07C211/27 , C07C215/52 , A61K31/135
CPC分类号： C07C215/54 , A61K31/00 , A61K31/137 , C07B2200/07 , C07C211/27 , C40B40/00
摘要： Neuroprotectant agents are provided which do not contain peptides and axe protected from the degradation that limits the use of peptide-based drugs in systemic circulation. With great selectivity for NMDA receptors, the agents exert an open channel block on NMDA receptors, and protect neuronal cells containing such receptors from excitatoxic cell death.
摘要翻译：提供的神经保护剂不含有限制肽系药物在体循环中使用的降解的肽和斧头。对NMDA受体具有很好的选择性，该试剂在NMDA受体上发挥开放通道阻断，并保护含有此类受体的神经元细胞免于兴奋性细胞死亡。

3. 发明授权

US5516890A Biologically mimetic synthetic ion channel transducers and methods of making the same 失效
标题翻译：生物模拟合成离子通道换能器及其制造方法
公开(公告)号：US5516890A
公开(公告)日：1996-05-14
申请号：US312821
申请日：1994-09-27
申请人： John Tomich , Mauricio Montal
发明人： John Tomich , Mauricio Montal
IPC分类号： C07K14/00 , C07K14/705 , C12Q1/00 , G01N33/543 , A61K38/04 , C07K5/00 , C07K7/00
CPC分类号： G01N33/5438 , C07K14/001 , C07K14/705 , C12Q1/002 , Y10S435/817 , Y10S436/806
摘要： The invention relates to synthetic proteins that can be used in in vitro sensing devices to detect the presence of physiologically active substances. The synthetic proteins are mimetic to native ion channels in mammalian systems. The invention also relates to a biosensor comprising a support assembly, a synthetic lipid bilayer containing the active channel protein. Lastly, the invention relates to the use of the biosensor disclosed in the application for the in vitro detection of physiologically active substances including antiseptics, antibiotics, neurotransmittors, and others.
摘要翻译：本发明涉及可用于体外感测装置以检测生理活性物质的存在的合成蛋白质。合成蛋白质是模拟哺乳动物系统中的天然离子通道。本发明还涉及包含支持组件，含有活性通道蛋白质的合成脂质双层的生物传感器。最后，本发明涉及在应用中公开的用于体外检测包括防腐剂，抗生素，神经递质等生理活性物质的生物传感器的用途。

4. 发明授权

US06251854B1 N-methyl-d-aspartate receptor channel blockers and method for identifying such 失效
标题翻译： N-甲基-D-天冬氨酸受体通道阻断剂及其鉴定方法
公开(公告)号：US06251854B1
公开(公告)日：2001-06-26
申请号：US09381434
申请日：1999-12-06
申请人： Mauricio Montal , Antonio Ferrer-Montiel , Jaime Merino , Sylvie Blondelle , Richard Houghten
发明人： Mauricio Montal , Antonio Ferrer-Montiel , Jaime Merino , Sylvie Blondelle , Richard Houghten
IPC分类号： A61K3800
CPC分类号： C07D487/04 , A61K31/4188 , A61K38/08 , C07K5/06095 , C07K5/0817 , C07K7/06
摘要： Compounds that provide protection against excitotoxic neuronal damage are selected from the group consisting of Arg-rich oligopeptides and compounds of formula 1: where R1 is alkyl, alkenyl, or hydroxyalkyl, aminoalkyl, or alkoxy-alkyl; and R2 and R3 are each natural or artificial amino acid side chains.
摘要翻译：提供针对兴奋性毒性神经元损伤的保护的化合物选自富含Arg的寡肽和式1的化合物：其中R 1是烷基，烯基或羟烷基，氨基烷基或烷氧基 - 烷基; R2和R3各自为天然或人造氨基酸侧链。

5. 发明授权

US5837265A Chemically-modified clostridiatoxin with improved properties 失效
标题翻译：化学修饰的梭菌毒素具有改善的性质
公开(公告)号：US5837265A
公开(公告)日：1998-11-17
申请号：US612571
申请日：1996-03-08
申请人： Mauricio Montal , Antonio Ferrer-Montiel
发明人： Mauricio Montal , Antonio Ferrer-Montiel
IPC分类号： A61K38/00 , A61K39/08 , C07K14/33 , A61K39/00 , A61K39/02 , A61K39/06
CPC分类号： C07K14/33 , A61K39/08 , A61K38/00 , Y10S424/832
摘要： The invention consists of modified Clostridium neurotoxin compounds, pharmaceutical compositions containing such compounds and methods for preparing such compounds. In particular, the compounds of the invention are purified Clostridium botulinum and Clostridium tetani neurotoxins in which the tyrosine residues have been modified to have a negative charge (e.g., by covalent attachment of a phosphate or sulphate thereto) or in which the tyrosine residues have been substituted with amino acids having a negative charge (e.g., glutamate, aspartate, or negatively charged, non-natural amino acids). Toxins having phosphorylated tyrosine residues in both the light and heavy chains of the toxins are preferred. Methods for enzymatic and chemical modification of tyrosine residues in purified Clostridium neurotoxins are provided.
摘要翻译：本发明由改良的梭状芽胞杆菌神经毒素化合物，含有这些化合物的药物组合物和制备这些化合物的方法组成。特别地，本发明的化合物是精制的肉毒梭菌和破伤风梭菌神经毒素，其中酪氨酸残基被修饰为具有负电荷（例如，通过共价连接磷酸盐或硫酸盐）或其中酪氨酸残基已被由具有负电荷的氨基酸（例如谷氨酸，天冬氨酸或带负电荷的非天然氨基酸）取代。在毒素的轻链和重链都具有磷酸化酪氨酸残基的毒素是优选的。提供了纯化的梭菌属神经毒素中酪氨酸残基酶促和化学修饰的方法。

6. 发明授权

US5368712A Biologically mimetic synthetic ion channel transducers 失效
标题翻译：生物模拟合成离子通道换能器
公开(公告)号：US5368712A
公开(公告)日：1994-11-29
申请号：US576222
申请日：1990-08-31
申请人： John Tomich , Mauricio Montal
发明人： John Tomich , Mauricio Montal
IPC分类号： C07K14/00 , C07K14/705 , C12Q1/00 , G01N33/543 , G01N27/327
CPC分类号： G01N33/5438 , C07K14/001 , C07K14/705 , C12Q1/002 , Y10S435/817 , Y10S436/806
摘要： The invention relates to synthetic proteins that can be used in in vitro sensing devices to detect the presence of physiologically active substances. The synthetic proteins are mimetic to native ion channels in mammalian systems. The invention also relates to a biosensor comprising a support assembly, a synthetic lipid bilayer containing the active channel protein. Lastly, the invention relates to the use of the biosensor disclosed in the application for the in vitro detection of physiologically active substances including antiseptics, antibiotics, neurotransmittors, and others.
摘要翻译：本发明涉及可用于体外感测装置以检测生理活性物质的存在的合成蛋白质。合成蛋白质是模拟哺乳动物系统中的天然离子通道。本发明还涉及包含支持组件，含有活性通道蛋白质的合成脂质双层的生物传感器。最后，本发明涉及在应用中公开的用于体外检测包括防腐剂，抗生素，神经递质等生理活性物质的生物传感器的用途。

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