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    Methods of ligating expressed proteins
    5.
    发明授权
    Methods of ligating expressed proteins 有权
    连接表达蛋白的方法

    公开(公告)号：US06875594B2

    公开(公告)日：2005-04-05

    申请号：US09904117

    申请日：2001-07-12

    申请人： Tom W. Muir ,  Philip A. Cole ,  Dolan Sondhi ,  Konstantine Severinov

    发明人： Tom W. Muir ,  Philip A. Cole ,  Dolan Sondhi ,  Konstantine Severinov

    IPC分类号： C12N9/12 ,  C12N9/00 ,  C07K14/00

    CPC分类号： C12N9/1205 ,  C07K2319/00

    摘要： The present invention provides a method of cleaving a recombinantly expressed protein from an intein and ligating the protein to a peptide containing an N-terminal cysteine having an unoxidized sulfhydryl side chain which comprises contacting the protein with the peptide in a reaction solution comprising a conjugated thiophenol, thereby forming a C-terminal thioester of the recombinant protein which spontaneously rearranges intramolecularly to form an amide bond linking the protein to the peptide. The present invention also provides a method of producing a protein-chip composition comprising the steps of: (a) contacting a solid support chip containing an amine group with a peptide containing an N-terminal cysteine having an unoxidized sulfhydryl side chain thereby covalently linking the peptide to the solid support, forming a peptide-chip; and (b) contacting a recombinant protein having an intein domain with the peptide-chip of step (a) with a reaction solution containing a conjugated thiophenol, thereby forming a C-terminal thioester of the recombinant protein which spontaneously rearranges intramoleculaly to form an amide bond covalently linking the protein to the peptide-chip, thereby producing a protein-chip composition.

    摘要翻译： 本发明提供了从内含肽切割重组表达的蛋白质并将蛋白质与包含具有未氧化的巯基侧链的N-末端半胱氨酸的肽连接的方法，该方法包括使蛋白质与肽在包含共轭苯硫酚 从而形成重组蛋白质的C末端硫酯，其自发地在分子内重排以形成将蛋白质与肽连接的酰胺键。 本发明还提供一种制备蛋白质芯片组合物的方法，其包括以下步骤：（a）使含有胺基的固体支持物质与含有具有未氧化的巯基侧链的N-末端半胱氨酸的肽接触，从而共价连接 肽与固体支持物，形成肽芯片; 和（b）将具有内含蛋白结构域的重组蛋白质与步骤（a）的肽芯片与含有共轭苯硫酚的反应溶液接触，从而形成重组蛋白质的C末端硫酯，其自发地重排分子内分子形成酰胺 键将蛋白质与肽片共价连接，从而产生蛋白质芯片组合物。

    Inhibitors of sorotonin N-acetyltransferase
    6.
    发明授权
    Inhibitors of sorotonin N-acetyltransferase 失效
    红霉素N-乙酰转移酶抑制剂

    公开(公告)号：US5990094A

    公开(公告)日：1999-11-23

    申请号：US14340

    申请日：1998-01-27

    申请人： Philip A. Cole ,  Ehab Khalil

    发明人： Philip A. Cole ,  Ehab Khalil

    IPC分类号： C07H19/20 ,  A61K31/70

    CPC分类号： C07H19/20

    摘要： This invention is directed to a compound having the formula I. ##STR1## This invention is directed to a pharmaceutical composition comprising a compound which inhibits serotonin N-acetyltransferase having the formula I and a pharmaceutical acceptable carrier. The present invention relates to novel compounds and analogs which inhibit the serotonin N-acetyltransferase enzyme, and to processes for their preparation.

    摘要翻译： 本发明涉及具有式I的化合物。本发明涉及一种药物组合物，其包含抑制具有式I的5-羟色胺N-乙酰基转移酶的化合物和药学上可接受的载体。 本发明涉及抑制5-羟色胺N-乙酰转移酶的新化合物和类似物及其制备方法。

    Bisbubstrate inhibitors of kinases
    9.
    发明授权
    Bisbubstrate inhibitors of kinases 失效
    双底物激酶抑制剂

    公开(公告)号：US07045617B2

    公开(公告)日：2006-05-16

    申请号：US09811870

    申请日：2001-03-21

    申请人： Philip A. Cole ,  Keykavous Parang ,  Ararat Abloogu ,  Ronald A. Kohanski ,  Aliya Courtney

    发明人： Philip A. Cole ,  Keykavous Parang ,  Ararat Abloogu ,  Ronald A. Kohanski ,  Aliya Courtney

    IPC分类号： C07H19/20 ,  A61K38/28 ,  A61K38/00 ,  A61K38/04

    CPC分类号： A61K47/62

    摘要： Protein kinase inhibitors have applications as anti-cancer therapeutic agents and biological tools in cell signalling. Potent and selective bisubstrate inhibitors for the insulin receptor tyrosine kinase are based on a phosphoryl transfer mechanism involving a dissociative transition state. One such inhibitor is synthesized by linking ATPγS to a peptide substrate analog via a two-carbon spacer. The compound is a high-affinity competitive inhibitor against both nucleotide and peptide substrate and shows a slow off-rate. A crystal structure of this inhibitor bound to the tyrosine kinase domain of the insulin receptor confirms the key design features inspired by a dissociative transition state, and reveal that the linker takes part in the octahedral coordination of an active site Mg2+ ion.

    摘要翻译： 蛋白激酶抑制剂可用作细胞信号传导中的抗癌治疗剂和生物工具。 用于胰岛素受体酪氨酸激酶的强效选择性双底物抑制剂是基于涉及离解过渡态的磷酰转移机制。 一种这样的抑制剂通过经由二碳间隔基连接ATPgammaS到肽底物类似物来合成。 该化合物是针对核苷酸和肽底物的高亲和力竞争性抑制剂，显示出缓慢的脱离率。 结合胰岛素受体的酪氨酸激酶结构域的这种抑制剂的晶体结构证实了由解离过渡状态启发的关键设计特征，并且揭示了连接体参与活性位点Mg 2+的八面体配位， / SUP>离子。

    COMPOSITIONS AND METHODS FOR TREATING FOXP3+ TREG RELATED DISEASES
    10.
    发明申请
    COMPOSITIONS AND METHODS FOR TREATING FOXP3+ TREG RELATED DISEASES 审中-公开
    用于治疗FOXP3 + TREG相关疾病的组合物和方法

    公开(公告)号：US20130323283A1

    公开(公告)日：2013-12-05

    申请号：US13991271

    申请日：2011-12-01

    申请人： Wayne W. Hancock ,  Steven M. Albelda ,  Philip A. Cole

    发明人： Wayne W. Hancock ,  Steven M. Albelda ,  Philip A. Cole

    IPC分类号： A61K31/4155 ,  A61K38/16 ,  A61K31/7076 ,  A61K39/00

    CPC分类号： A61K31/4155 ,  A61K31/7076 ,  A61K38/16 ,  A61K39/0011 ,  G01N33/5011 ,  G01N33/505 ,  A61K2300/00

    摘要： Methods for treating or preventing a Foxp3+ T regulatory cell (Treg) related disease in a subject in need thereof comprise administering to the subject an effective amount of a pharmaceutical composition comprising an inhibitor of a histone/protein acetyltransferase (HAT). Methods for identifying an agent useful for treating or preventing a Foxp3+ T regulatory cell (Treg) related disease comprise (a) contacting a candidate agent with a test sample comprising Foxp3+ T regulatory cells (Tregs), and (b) comparing a function of the Foxp3+ Tregs in the test sample with that in a control sample, wherein inhibition of the function of the Foxp3+ Tregs in the test sample when compared with the control sample indicates that the candidate agent is an agent useful for treating or preventing a Foxp3+ Treg related disease.

    摘要翻译： 在有需要的受试者中治疗或预防Foxp3 + T调节细胞（Treg）相关疾病的方法包括向受试者施用有效量的包含组蛋白/蛋白质乙酰转移酶（HAT）抑制剂的药物组合物。 用于鉴定可用于治疗或预防Foxp3 + T调节细胞（Treg）相关疾病的药剂的方法包括（a）使候选药剂与包含Foxp3 + T调节细胞（Treg）的测试样品接触，和（b）比较 测试样品中的Foxp3 + Treg与对照样品中的Foxp3 + Treg相比，其中与对照样品相比，测试样品中Foxp3 + Treg的功能的抑制表明候选试剂是可用于治疗或预防Foxp3 + Treg相关疾病的药剂 。