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    Method for forming an amino acid thiohydantoin using an N-substituted ketenimine activator
    1.
    发明授权
    Method for forming an amino acid thiohydantoin using an N-substituted ketenimine activator 失效
    使用N-取代的酮亚胺激活剂形成氨基酸硫代乙内酰脲的方法

    公开(公告)号：US5051368A

    公开(公告)日：1991-09-24

    申请号：US546303

    申请日：1990-06-29

    申请人： Victoria L. Boyd ,  David H. Hawke ,  Timothy G. Geiser

    发明人： Victoria L. Boyd ,  David H. Hawke ,  Timothy G. Geiser

    IPC分类号： C07D233/72 ,  C07D233/86 ,  C07K1/12 ,  C07K5/06 ,  G01N33/68

    CPC分类号： G01N33/6821 ,  C07K1/12 ,  Y10S530/81 ,  Y10T436/25125 ,  Y10T436/255

    摘要： A method of forming an amino acid thiohydantoin from an N-protected amino acid or the C-terminal amino acid of an N-protected peptide. The amino acid is activated by reaction with a ketenimine, and the activated ester is converted to the thiohydantoin by reaction with silyl or pyridine isothiocyanate. The ketenimine is generated by treating an N-substituted isoxazolium compound, such as Woodwards Reagent K with a base, preferably in the presence of the amino acid. Also disclosed is a solid phase support having a derivatized N-substituted isoxazolium or ketenimine group for use in the method.

    摘要翻译： 由N-保护的氨基酸或N-保护肽的C-末端氨基酸形成氨基酸硫代乙内酰脲的方法。 氨基酸通过与酮亚胺反应而活化，活化酯通过与甲硅烷基或吡啶异硫氰酸酯反应而转化为硫代乙内酰脲。 通过用碱处理N-取代的异恶唑鎓化合物，例如Woodwards Reagent K，优选在氨基酸存在下生成酮亚胺。 还公开了具有用于该方法的衍生化的N-取代的异恶唑或酮亚胺基的固相载体。

    Automated polypeptide synthesis apparatus
    3.
    发明授权
    Automated polypeptide synthesis apparatus 失效
    自动多肽合成仪

    公开(公告)号：US5186898A

    公开(公告)日：1993-02-16

    申请号：US328488

    申请日：1989-03-24

    申请人： John Bridgham ,  Timothy G. Geiser ,  Michael W. Hunkapiller ,  Stephen B. H. Kent ,  Mark P. Marriott ,  Paul O. Ramstad ,  Eric S. Nordman

    发明人： John Bridgham ,  Timothy G. Geiser ,  Michael W. Hunkapiller ,  Stephen B. H. Kent ,  Mark P. Marriott ,  Paul O. Ramstad ,  Eric S. Nordman

    IPC分类号： B01J19/00 ,  C07K1/04 ,  C40B40/10 ,  C40B60/14

    CPC分类号： C07K1/045 ,  B01J19/0046 ,  B01J2219/00286 ,  B01J2219/00389 ,  B01J2219/00484 ,  B01J2219/00488 ,  B01J2219/0049 ,  B01J2219/00495 ,  B01J2219/005 ,  B01J2219/0059 ,  B01J2219/00596 ,  B01J2219/00689 ,  B01J2219/00695 ,  B01J2219/00725 ,  C40B40/10 ,  C40B60/14 ,  Y10S436/81

    摘要： An apparatus is provided for automatically constructing a polypeptide of high purity, up to 50 amino acids in length, using only single couplings. The apparatus includes an activation system for receiving protected amino acids, one kind at a time, having a common vessel (an activator vessel) in which to activate each of the amino acids. Also included is a reaction vessel for containing a resin used in solid-phase peptide synthesis for attaching a peptide chain thereto. A transfer system is also provided, which operates under control of a computer, to transfer the activated species from the activation system to the reaction vessel and to transfer amino acids, reagents, gases, and solvents from one part of the apparatus to another. The activator system also includes a temperature controlled concentrator vessel in which an activator solvent is replaced by a coupling solvent to enhance the coupling of the activated species to the peptide chain in the reaction vessel. Also included in the synthesizer system is a vortexer for affecting total washing of materials in the reaction vessel and the reaction vessel itself, an automated peptide resin sampling system, and an autodelivery system for providing individual containers of amino acid to the synthesizer in the order desired in the peptide sequence. A liquid sensor system is also included to monitor transitions between gases and liquids in specific tubes in the synthesizer in order to provide input signals to the computer system for control purposes. The computer system software which controls the operation of the synthesizer is organized according to a series of menus which allows the user of the system to select individual cycles of operation for each vessel in the synthesizer. In addition, an algorithm has been developed which provides for optimum efficiency in tbe production of a peptide for any given selection of cycles.

    摘要翻译： 提供了一种用于仅使用单个耦合自动构建高纯度多达50个氨基酸长度的多肽的装置。 该装置包括用于一次接收受保护的氨基酸的激活系统，其具有在其中激活每个氨基酸的共同血管（活化剂容器）。 还包括用于含有固相肽合成中用于连接肽链的树脂的反应容器。 还提供了在计算机控制下操作的转移系统，以将活化物质从活化系统转移到反应容器中，并将氨基酸，试剂，气体和溶剂从设备的一部分转移到另一部分。 活化剂体系还包括温度控制的浓缩容器，其中活化剂溶剂被偶联溶剂代替以增强活化物质与反应容器中的肽链的偶联。 还包括在合成器系统中的是用于影响反应容器和反应容器本身中的材料的全部洗涤的涡流器，自动化肽树脂取样系统和用于按合适的顺序向合成器提供单个氨基酸容器的自动输送系统 在肽序列中。 还包括液体传感器系统以监测合成器中特定管中的气体和液体之间的转换，以便为控制目的向计算机系统提供输入信号。 控制合成器操作的计算机系统软件根据一系列菜单进行组织，这些菜单允许系统的用户为合成器中的每个容器选择各个操作周期。 此外，已经开发了一种算法，其为任何给定的循环选择提供肽的生产的最佳效率。

    Automated polypeptide synthesis process
    6.
    发明授权
    Automated polypeptide synthesis process 失效
    自动多肽合成过程

    公开(公告)号：US4816513A

    公开(公告)日：1989-03-28

    申请号：US53324

    申请日：1987-05-22

    申请人： John Bridgham ,  Timothy G. Geiser ,  Michael W. Hunkapiller ,  Stephen B. H. Kent ,  Mark P. Marriott ,  Paul O. Ramstad ,  Eric S. Nordman

    发明人： John Bridgham ,  Timothy G. Geiser ,  Michael W. Hunkapiller ,  Stephen B. H. Kent ,  Mark P. Marriott ,  Paul O. Ramstad ,  Eric S. Nordman

    IPC分类号： C07K1/00 ,  B01J19/00 ,  C07K1/04 ,  C40B40/10 ,  C40B60/14 ,  C08L89/00 ,  C07C103/52

    CPC分类号： C07K1/045 ,  B01J19/0046 ,  B01J2219/00286 ,  B01J2219/00389 ,  B01J2219/00484 ,  B01J2219/00488 ,  B01J2219/0049 ,  B01J2219/00495 ,  B01J2219/005 ,  B01J2219/0059 ,  B01J2219/00596 ,  B01J2219/00689 ,  B01J2219/00695 ,  B01J2219/00725 ,  C40B40/10 ,  C40B60/14

    摘要： An apparatus is provided for automatically constructing a polypeptide of high purity, up to 50 amino acids in length, using only single couplings. The apparatus includes an activation system for receiving protected amino acids, one kind at a time, having a common vessel (an activator vessel) in which to activate each of the amino acids. Also included is a reaction vessel for containing a resin used in solid-phase peptide synthesis for attaching a peptide chain thereto. A transfer system is also provided, which operates under control of a computer, to transfer the activated species from the activation system to the reaction vessel and to transfer amino acids, reagents, gases, and solvents from one part of the apparatus to another. The activator system also includes a temperature controlled concentrator vessel in which an activator solvent is replaced by a coupling solvent to enhance the coupling of the activated species to the peptide chain in the reaction vessel. Also included in the synthesizer system is a vortexer for affecting total washing of materials in the reaction vessel and the reaction vessel itself, an automated peptide resin sampling system, and an autodelivery system for providing individual containers of amino acid to the synthesizer in the order desired in the peptide sequence. A liquid sensor system is also included to monitor transitions between gases and liquids in specific tubes in the synthesizer in order to provide input signals to the computer system for control purposes. The computer system software which controls the operation of the synthesizer is organized according to a series of menus which allows the user of the system to select individual cycles of operation for each vessel in the synthesizer. In addition, an algorithm has been developed which provides for optimum efficiency in the production of a peptide for any given selection of cycles.

    摘要翻译： 提供了一种用于仅使用单个耦合自动构建高纯度多达50个氨基酸长度的多肽的装置。 该装置包括用于一次接收受保护的氨基酸的激活系统，其具有在其中激活每个氨基酸的共同血管（活化剂容器）。 还包括用于含有固相肽合成中用于连接肽链的树脂的反应容器。 还提供了在计算机控制下操作的转移系统，以将活化物质从活化系统转移到反应容器中，并将氨基酸，试剂，气体和溶剂从设备的一部分转移到另一部分。 活化剂体系还包括温度控制的浓缩容器，其中活化剂溶剂被偶联溶剂代替以增强活化物质与反应容器中的肽链的偶联。 还包括在合成器系统中的是用于影响反应容器和反应容器本身中的材料的全部洗涤的涡流器，自动化肽树脂取样系统和用于按合适的顺序向合成器提供单个氨基酸容器的自动输送系统 在肽序列中。 还包括液体传感器系统以监测合成器中特定管中的气体和液体之间的转换，以便为控制目的向计算机系统提供输入信号。 控制合成器操作的计算机系统软件根据一系列菜单进行组织，这些菜单允许系统的用户为合成器中的每个容器选择各个操作周期。 此外，已经开发了一种算法，其提供用于任何给定选择周期的肽的生产的最佳效率。

    Reduced Interference from Single Strand Binding Proteins
    7.
    发明申请
    Reduced Interference from Single Strand Binding Proteins 审中-公开
    降低单链结合蛋白的干扰

    公开(公告)号：US20110318740A1

    公开(公告)日：2011-12-29

    申请号：US13149697

    申请日：2011-05-31

    申请人： Robert G. Eason ,  Timothy G. Geiser ,  Vladimir I. Bashkirov ,  Kristian M. Scaboo

    发明人： Robert G. Eason ,  Timothy G. Geiser ,  Vladimir I. Bashkirov ,  Kristian M. Scaboo

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6816 ,  C12Q1/6846 ,  C12Q2522/101 ,  C12Q2561/109 ,  C12Q2565/519 ,  C12Q1/686

    摘要： Disclosed, for example, are methods for detecting at least one target polynucleotide comprising cleaving a flap from a polynucleotide probe that is hybridized to a complementary target polynucleotide, and hybridizing the cleaved flap to a complementary capture probe immobilized on a surface, wherein said cleaving and/or hybridizing occurs in the presence of a single strand binding protein that is capable of binding single-stranded DNA, but that can bind neither the flap nor the capture probe. The cleaved flap and the complementary capture probe may each comprise PNA, RNA, LNA, L-DNA or other modified nucleotides or chimeras thereof that do not significantly bind to the single strand binding protein.

    摘要翻译： 例如，公开了用于检测至少一种靶多核苷酸的方法，所述至少一种靶多核苷酸包括从互补靶多核苷酸杂交的多核苷酸探针切割瓣，并将切割的瓣与固定在表面上的互补捕获探针杂交，其中所述切割和 /或杂交发生在能够结合单链DNA的单链结合蛋白存在下，但是既不结合皮瓣也不能结合捕获探针。 切割的瓣和互补捕获探针可以各自包含不显着结合单链结合蛋白的PNA，RNA，LNA，L-DNA或其它修饰的核苷酸或嵌合体。