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    Agitation stabilizer in solid-phase peptide synthesizer
    1.
    发明授权
    Agitation stabilizer in solid-phase peptide synthesizer 失效
    固相肽合成仪中的搅拌稳定剂

    公开(公告)号：US5344613A

    公开(公告)日：1994-09-06

    申请号：US9080

    申请日：1993-01-26

    申请人： Kiyoshi Nokihara ,  Rintaro Yamamoto ,  Makoto Hazama ,  Shin Nakamura

    发明人： Kiyoshi Nokihara ,  Rintaro Yamamoto ,  Makoto Hazama ,  Shin Nakamura

    IPC分类号： B01J19/00 ,  B01L99/00 ,  C07K1/04 ,  C08F2/00 ,  C40B40/10 ,  C40B60/14 ,  C07K5/00

    CPC分类号： B01L99/00 ,  B01J19/0046 ,  C07K1/045 ,  B01J2219/00286 ,  B01J2219/00288 ,  B01J2219/005 ,  B01J2219/0059 ,  B01J2219/00596 ,  B01J2219/00725 ,  C40B40/10 ,  C40B60/14

    摘要： In an automated solid-phase peptide synthesizing apparatus comprising at least one reaction vessel containing particulate resin as an insoluble support matrix which anchors elongating peptide chains yielded through coupling-assembly formation of peptide bonds, mixing agitation of reagents, as well as circulation agitation of washing solvents flushing the coupling-associated reaction solutions, introduced in peptide chain-assembly process steps into the reaction vessel, is effected by the bubbling of an inert gas forcibly passed through the reagents or washing solvent via a drainage port of the reaction vessel, in order to promote peptide synthesis. A removable agitation stabilizer is inserted into the reaction vessel as a barrier for inhibiting extra-vessel escape, due to action of the bubbling inert gas, of the reagents as well as the washing solvents, and of the support matrix anchoring the elongating peptide chains. The stabilizer also breaks clumping and coagulative skinning of elongated peptides bound to the support matrix, as effects further consequent of the action of the bubbling inert gas and levitated thereby toward the mouth of the reaction vessel during peptide synthesis. The stabilizer additionally acts as a baffle furthering mixing agitation, to promote dispersive mixing of the peptidyl resin with the reagents and washing solvents during peptide chain assembly; and It also serves to distribute washing solvents evenly along the inner surface of the reaction vessel.

    摘要翻译： 在一种自动化固相肽合成装置中，包括至少一个含有颗粒状树脂作为不溶性支持基质的反应容器，该反应容器通过肽键的偶联 - 组装形成固定延伸的肽链，混合搅拌试剂以及循环搅拌洗涤 将通过肽链组装工艺步骤引入反应容器的偶联相关反应溶液冲洗到反应容器中，通过以反应容器的排水口强制通过试剂或洗涤溶剂的惰性气体起泡 促进肽合成。 将可移除的搅拌稳定剂插入到反应容器中，作为阻止由于起泡惰性气体的作用以及洗涤溶剂和固定伸长肽链的载体基质而导致的外部容器逸出的屏障。 稳定剂还破坏结合到载体基质上的细长肽的结块和凝结性皮肤剥离，其作用是由于气泡惰性气体的作用而进一步引起，并且由此在肽合成期间悬浮于反应容器口中。 稳定剂另外作为进一步混合搅拌的挡板，以促进肽链组装期间肽基树脂与试剂和洗涤溶剂的分散混合; 并且还用于沿着反应容器的内表面均匀分布洗涤溶剂。

    Apparatus for isolation of synthetic peptide without mechanical loss
    2.
    发明授权
    Apparatus for isolation of synthetic peptide without mechanical loss 失效
    无机械损失分离合成肽的装置

    公开(公告)号：US5356596A

    公开(公告)日：1994-10-18

    申请号：US22036

    申请日：1993-02-24

    申请人： Kiyoshi Nokihara ,  Rintaro Yamamoto ,  Shin Nakamura

    发明人： Kiyoshi Nokihara ,  Rintaro Yamamoto ,  Shin Nakamura

    IPC分类号： B01J19/00 ,  C07K1/04 ,  C08F2/00 ,  C40B40/10 ,  C40B50/14 ,  C40B60/14 ,  B01L3/00 ,  C12M1/00

    CPC分类号： C07K1/045 ,  B01J19/0046 ,  B01J2219/00286 ,  B01J2219/00288 ,  B01J2219/00308 ,  B01J2219/00454 ,  B01J2219/005 ,  B01J2219/00725 ,  C40B40/10 ,  C40B50/14 ,  C40B60/14

    摘要： In connection with an automated peptide synthesizer, an apparatus and associated method through which peptides produced in simultaneous multiple synthesis are together isolable. Cleavage to liberate the peptides from linkage to the support matrix of the solid phase is carried out in the same vessels in which the synthesizing reactions took place. Prior to cleavage, a drainage port of each reaction vessel is closed off by a cap. The reaction vessel is inserted into a centrifuge tube, which in turn is put into a rack supporting a number of tubes equal to the number of channels of the peptide synthesizing apparatus. After the peptides are cleaved and dissolved into cleaving solution added into each of the reaction vessels, the caps are removed from the drainage ports of each reaction vessel, and the vessel is returned into the centrifuge tube. A plastic jet-fitting attached to the nozzle tip of a blow unit pressure gun is inserted into and pressed into contact against the supply opening of the reaction vessel. Operating a trigger of the pressure gun releases pressurized inert gas into the reaction chamber. The peptide-dissolved cleaving solution is thereby passed through the drainage port, and is thus transferred in liquid phase into the centrifuge tube as filtrate. Associated with the blow unit pressure gun, a needle tube fitting is provided for localized desiccation of wetted peptide following precipitation and centrifuging.

    摘要翻译： 关于自动肽合成仪，同时多重合成中产生的肽一起可分离的装置和相关方法。 在与发生合成反应的相同的容器中进行从固定相的支持基质的连接释放肽的切割。 在切割之前，每个反应容器的排水口由盖封闭。 将反应容器插入到离心管中，该离心管又被放入支架中，该支架中的多个管等于肽合成装置的通道数。 在肽被切割并溶解到每个反应容器中的裂解溶液中之后，从每个反应容器的排出口移除盖子，并将容器返回到离心管中。 将附接到吹塑单元压力枪的喷嘴尖端的塑料喷射管插入并压接到反应容器的供应开口。 操作压力枪的触发器将加压的惰性气体释放到反应室中。 因此，肽溶解的解离溶液通过排出口，因此以液相方式转移到作为滤液的离心管中。 与吹气单元压力枪相关联，提供针管配件，用于沉淀和离心后的湿肽的局部干燥。

    Method for peptide C-terminal fragment sequence analysis and apparatus for collecting peptide fragment
    4.
    发明授权
    Method for peptide C-terminal fragment sequence analysis and apparatus for collecting peptide fragment 失效
    肽C-末端片段序列分析方法及收集肽片段的方法

    公开(公告)号：US5470703A

    公开(公告)日：1995-11-28

    申请号：US136761

    申请日：1993-10-15

    申请人： Kiyoshi Nokihara ,  Rintaro Yamamoto

    发明人： Kiyoshi Nokihara ,  Rintaro Yamamoto

    IPC分类号： C07K1/12 ,  C12Q1/37 ,  G01N33/68 ,  C12Q1/00 ,  C12M1/40 ,  C12N11/00

    CPC分类号： C12Q1/37 ,  C07K1/128 ,  G01N33/6821 ,  Y10S436/81 ,  Y10T436/255

    摘要： The present invention relates to a method for peptide C-terminal fragment sequence analysis, in which the fragment collection is carried out on an allylamine group-derivatized polymer membrane or on allylamine group-derivatized glass fiber filter paper; the collected C-terminal fragment is immobilized thereon using a water-soluble carbodiimide etc.; and the obtained immobilized product is subjected directly to amino acid sequence analysis. The present invention also relates to an apparatus for collecting a peptide fragment. According to the method of the present invention, peptides which are rich in hydrophobic groups in their C-terminus and are therefore difficult to trap with polyvalent ion carriers, currently used in the gas-phase sequencer, can be completely analyzed up to their C-terminus. Also, amino acid sequence analysis can be made even when the amount of C-terminal fragments is very small. In addition, since collection and immobilization of fragments can be done in the same bottle, the risks of contamination and mechanical loss are very low.

    摘要翻译： 本发明涉及一种肽C-末端片段序列分析方法，其中片段收集是在烯丙基胺基衍生的聚合物膜上或在烯丙胺基衍生的玻璃纤维滤纸上进行的; 收集的C-末端片段使用水溶性碳二亚胺等固定在其上; 将获得的固定化产物直接进行氨基酸序列分析。 本发明还涉及一种收集肽片段的装置。 根据本发明的方法，可以完全分析其C-末端富含疏水性基团并且因此难以与当前用于气相测序仪中的多价离子载体捕获的肽， 终点。 此外，即使C末端片段的量非常小，也可以进行氨基酸序列分析。 此外，由于碎片的收集和固定可以在同一瓶中进行，污染和机械损失的风险非常低。

    Apparatus for collecting peptide fragment
    5.
    发明授权
    Apparatus for collecting peptide fragment 失效
    用于收集肽片段的装置

    公开(公告)号：US5431882A

    公开(公告)日：1995-07-11

    申请号：US154515

    申请日：1993-11-19

    申请人： Kiyoshi Nokihara ,  Rintaro Yamamoto ,  Yoshiyuki Togawa ,  Mitsuhiro Hashimoto ,  Naoki Morita

    发明人： Kiyoshi Nokihara ,  Rintaro Yamamoto ,  Yoshiyuki Togawa ,  Mitsuhiro Hashimoto ,  Naoki Morita

    IPC分类号： C07K1/14 ,  C07K1/12 ,  G01N33/68

    CPC分类号： G01N33/6803 ,  C07K1/12

    摘要： The present invention relates to an apparatus for collecting a peptide fragment, wherein a C-terminal peptide fragment is collected from a peptide fragment mixture resulting from specific cleavage of the peptide bond between a lysine residue and the C-terminal amino acid residue adjacent thereto. The apparatus has an immobilizing means, a cleaving means, a recovering means and a control means. According to the present invention, since the control means sequentially executes the immobilizing means, cleaving means and recovering means, no skillful work is required in peptide fragment collection, making it possible to collect the carboxyl-terminal peptide fragment with simple operation and high reproducibility.

    摘要翻译： 本发明涉及一种用于收集肽片段的装置，其中从由赖氨酸残基和与其相邻的C末端氨基酸残基之间的肽键的特异性切割得到的肽片段混合物收集C末端肽片段。 该装置具有固定装置，切割装置，恢复装置和控制装置。 根据本发明，由于控制装置依次执行固定装置，切割装置和恢复装置，因此在肽片段收集中不需要熟练的工作，使得可以以简单的操作和高再现性收集羧基末端肽片段。

    Method for amino acid sequence analysis
    6.
    发明授权
    Method for amino acid sequence analysis 失效
    氨基酸序列分析方法

    公开(公告)号：US5234836A

    公开(公告)日：1993-08-10

    申请号：US841797

    申请日：1992-02-26

    申请人： Kiyoshi Nokihara ,  Koji Muramoto

    发明人： Kiyoshi Nokihara ,  Koji Muramoto

    IPC分类号： G01N21/78 ,  G01N30/06 ,  G01N30/74 ,  G01N30/88 ,  G01N33/68

    CPC分类号： G01N33/6824

    摘要： The present invention is directed to a method for amino acid sequence analysis comprising either the steps of labeling the sample with a fluorescent reagent and quenching the excess fluorescent reagent remaining after said labeling with an ammonium salt, or the steps of degrading amino acid from the amino terminus of peptides or proteins using a fluorescent Edman reagent and quenching the excess fluorescent Edman reagent remaining after said degrading with an ammonium salt. The method of the present invention makes it possible to eliminate the interference of identification by the chromatographic peak of fluorescent reagent by quenching the excess fluorescent reagent in the sample.

    ANTIOXIDANT AGENT
    7.
    发明申请
    ANTIOXIDANT AGENT 审中-公开
    抗氧化剂

    公开(公告)号：US20110319347A1

    公开(公告)日：2011-12-29

    申请号：US13255551

    申请日：2010-03-11

    申请人： Kiyoshi Nokihara ,  Naeko Miyazato

    发明人： Kiyoshi Nokihara ,  Naeko Miyazato

    IPC分类号： A61K8/64 ,  C07K5/097 ,  A61Q19/02 ,  A61K38/07 ,  C07K5/117 ,  A61L2/00 ,  C07D213/68 ,  C07K5/087

    CPC分类号： A61K31/4412 ,  A61K8/4926 ,  A61K8/64 ,  A61K38/00 ,  A61K2800/522 ,  A61Q19/02 ,  C07K5/0808 ,  C07K5/0812 ,  C07K5/0817 ,  C07K5/0821 ,  C07K5/0823 ,  C07K5/1024

    摘要： Disclosed is an antioxidant which can exhibit a higher antioxidant ability than known antioxidative peptides. The antioxidant according to the present invention comprises mimosine and/or a mimosine-containing peptide(s). The mimosine-containing peptide is a peptide which comprises at least one mimosine residue in its amino acid sequence. Mimosine has stronger antioxidant potency than known antioxidative tripeptides even when used as it is alone, and therefore is useful as an antioxidant. In addition, the antioxidant action of a peptide can be increased by introducing mimosine thereinto, thereby obtaining a peptide with higher antioxidant potency than the original one.

    摘要翻译： 公开了一种抗氧化剂，其可以表现出比已知的抗氧化肽更高的抗氧化能力。 根据本发明的抗氧化剂包含含有肌动蛋白和/或含有含有嗜好肽的肽。 含有含mimosine的肽是在其氨基酸序列中包含至少一个mimosine残基的肽。 即使在单独使用时，肌酐具有比已知的抗氧化三肽更强的抗氧化能力，因此可用作抗氧化剂。 此外，通过在其中引入含有肌动蛋白的方法可以增加肽的抗氧化作用，从而获得比原来更高的抗氧化剂效能的肽。

    Biochip substrate and biochip
    8.
    发明申请
    Biochip substrate and biochip 有权
    生物芯片基板和生物芯片

    公开(公告)号：US20100130380A1

    公开(公告)日：2010-05-27

    申请号：US11922108

    申请日：2006-06-16

    申请人： Kiyoshi Nokihara ,  Yasuo Oka

    发明人： Kiyoshi Nokihara ,  Yasuo Oka

    IPC分类号： C40B40/00 ,  C40B60/14 ,  C40B50/00

    CPC分类号： G01N33/54393 ,  B01L3/5085 ,  B01L2200/12 ,  B01L2300/0636 ,  B01L2300/0829 ,  B01L2300/0893 ,  B01L2300/0896 ,  B01L2300/12 ,  B82Y30/00 ,  C40B60/14

    摘要： A biochip substrate which is free from cross-contamination due to spot spreading or contact with spots adjacent to each other, and a biochip using the same. A biochip substrate on which multiple valleys for immobilizing biological substances are formed so as to prevent cross-contamination due to spot spreading or contact with spots adjacent to each other, and a biochip using the same are provided. Moreover, it is found out that a desired binding in a target molecule contained in a test sample occurs at a detectable level in a solution system even in the case where a valley have such a small capacity as 1 nL to 10 nL.

    摘要翻译： 一种生物芯片基板，其由于点扩散或与彼此相邻的点接触而没有交叉污染，并且使用该生物芯片。 其上形成有用于固定生物物质的多个谷的生物芯片基板，以防止由于点扩散或彼此相邻的点的接触而产生的交叉污染，并且提供了使用该生物体的生物芯片。 此外，发现测试样品中包含的靶分子中期望的结合在溶液体系中发生在可检测的水平，即使在谷具有如1nL至10nL这样小的容量的情况下也是如此。

    Dibenzosuberyl and dibenzosuberenyl derivatives
    9.
    发明授权
    Dibenzosuberyl and dibenzosuberenyl derivatives 失效
    二苄青霉素和二苯并环丁基衍生物

    公开(公告)号：US5442122A

    公开(公告)日：1995-08-15

    申请号：US145101

    申请日：1993-11-03

    申请人： Masaki Noda ,  Kiyoshi Nokihara

    发明人： Masaki Noda ,  Kiyoshi Nokihara

    IPC分类号： C07C235/08 ,  C07C217/74 ,  C07C235/12 ,  C07C237/08 ,  C07C237/12 ,  C07C237/22 ,  C07C271/24 ,  C07K1/04 ,  C07C211/00

    CPC分类号： C07C271/24 ,  C07C217/74 ,  C07K1/042 ,  C07C2103/18 ,  C07C2103/32 ,  Y10S530/816

    摘要： The present invention is directed to a compound represented by the following formula (I), ##STR1## and a linker for peptide synthesis using the above compound. When the linker of the present invention is used for the solid-phase peptide synthesis, it is possible to synthesize those peptides which are sensitive to acid and difficult to synthesize by conventional methods. Also, side reactions can be prevented, and the desired product is produced at a high purity because cleavage can be achieved under milder conditions or in shorter times. In other words, efficient peptide synthesis is possible.

    摘要翻译： 本发明涉及由下式（I）表示的化合物，（I）和使用上述化合物的肽合成接头。 当本发明的接头用于固相肽合成时，可以通过常规方法合成那些对酸敏感并难以合成的那些肽。 此外，可以防止副反应，并且所需产物以高纯度制备，因为在较温和的条件下或在较短时间内可以实现切割。 换句话说，有效的肽合成是可能的。