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    Peptides and compounds that bind to the IL-1 receptor
    51.
    发明授权
    Peptides and compounds that bind to the IL-1 receptor 失效
    结合IL-1受体的肽和化合物

    公开(公告)号：US5861476A

    公开(公告)日：1999-01-19

    申请号：US464538

    申请日：1995-06-05

    申请人： Ronald W. Barrett ,  Stephen D. Yanofsky ,  David Baldwin ,  Jeff W. Jacobs ,  Phillipe R. Bovy ,  Ellen M. Leahy ,  Richard S. Pottorf

    发明人： Ronald W. Barrett ,  Stephen D. Yanofsky ,  David Baldwin ,  Jeff W. Jacobs ,  Phillipe R. Bovy ,  Ellen M. Leahy ,  Richard S. Pottorf

    IPC分类号： A61K38/00 ,  C07K14/545 ,  C07K7/04 ,  A61K38/04

    CPC分类号： C07K14/545 ,  A61K38/00 ,  Y10S930/141

    摘要： Peptides that bind to the interleukin-1 type I receptor (IL-1RtI) can be used to assay the amount of IL-1R, or an IL-1R agonist or antagonist, in a sample and comprise a sequence of amino acids selected from the group consisting of (1) WXXXGZ.sub.1 W where Z.sub.1 is L, I, A, or Q; (2) XXQZ.sub.5 YZ.sub.6 XX where Z.sub.5 is P or Aze where Aze is azetidine; and Z.sub.6 is S, A, V, or L; and (3) Z.sub.23 NZ.sub.24 SZ.sub.25 Z.sub.26 Z.sub.27 Z.sub.28 Z.sub.29 Z.sub.30 L where Z.sub.23 is D or Y; Z.sub.24 is D or S; Z.sub.25 is S or W; Z.sub.26 is S or Y; Z.sub.27 is D or V; Z.sub.28 is S or W; Z.sub.29 is F or L; and Z.sub.30 is D or L; and where each amino acid is indicated by standard one letter abbreviation; and each X can be selected from any one of the 20 genetically coded L-amino acids or the stereoisomeric D-amino acids. Also provided are peptides which bind to the IL-1RtI, which are 11 to 40 amino acids in length, which comprise the core sequence of amino acids:Z.sub.31 XWZ.sub.32 Z.sub.33 Z.sub.34 Z.sub.35 Z.sub.36 QZ.sub.37 Z.sub.38where each letter represents the standard one letter abbreviation for an amino acid or an analog thereof; X is selected from the group of natural or unnatural amino acids; Z.sub.37 is a natural or unnatural cyclic amino acid; Z.sub.31 is selected from phenylalanine and acetylated phenylalanine; Z.sub.32 is a natural or unnatural amino acid; Z.sub.33 is selected from proline and pipecolic acid; Z.sub.34 is selected from glycine, d-alanine, d-valine, sarcosine and aminoisobutyric acid; Z.sub.35 is a natural or unnatural amino acid and Z.sub.36 is selected from tyrosine, phosphotyrosine, phenylalanine and tryptophan; and Z.sub.38 is selected from tyrosinamide and substituted tyrosinamide.

    摘要翻译： 结合白细胞介素-1 I型受体（IL-1RtI）的肽可用于测定样品中IL-1R或IL-1R激动剂或拮抗剂的量，并且包含选自以下的氨基酸序列： 由（1）WXXXGZ1W组成的组，其中Z1是L，I，A或Q; （2）XXQZ5YZ6XX其中Z5为P或Aze，其中Aze为氮杂环丁烷; Z6为S，A，V或L; 和（3）Z23NZ24SZ25Z26Z27Z28Z29Z30L其中Z23为D或Y; Z24是D或S; Z25为S或W; Z26为S或Y; Z27为D或V; Z28为S或W; Z29为F或L; Z30为D或L; 并且其中每个氨基酸由标准单字母缩写指示; 并且每个X可以选自20个遗传编码的L-氨基酸或立体异构体D-氨基酸中的任一个。 还提供了与IL-1RtI结合的肽，其长度为11至40个氨基酸，其包含氨基酸的核心序列：Z31XWZ32Z33Z34Z35Z36QZ37Z38，其中每个字母表示氨基酸或其类似物的标准单字母缩写; X选自天然或非天然氨基酸组; Z37是天然或非天然环状氨基酸; Z31选自苯丙氨酸和乙酰化苯丙氨酸; Z32是天然或非天然氨基酸; Z33选自脯氨酸和哌啶酸; Z34选自甘氨酸，d-丙氨酸，d-缬氨酸，肌氨酸和氨基异丁酸; Z35是天然或非天然氨基酸，Z36选自酪氨酸，磷酸酪氨酸，苯丙氨酸和色氨酸; Z38选自酪氨酰胺和取代的酪氨酰胺。

    Spatially-addressable immobilization of anti-ligands on surfaces
    53.
    发明授权
    Spatially-addressable immobilization of anti-ligands on surfaces 失效
    表面上抗配体的空间可寻址固定

    公开(公告)号：US5451683A

    公开(公告)日：1995-09-19

    申请号：US53124

    申请日：1993-04-23

    申请人： Ronald W. Barrett ,  Michael C. Pirrung ,  Lubert Stryer ,  Christopher P. Holmes ,  Steven A. Sundberg

    发明人： Ronald W. Barrett ,  Michael C. Pirrung ,  Lubert Stryer ,  Christopher P. Holmes ,  Steven A. Sundberg

    IPC分类号： C07D233/38 ,  C07D491/048 ,  C07D495/04 ,  C40B40/06 ,  G01N33/543 ,  G01N33/552 ,  A61K31/415

    CPC分类号： C07D495/04 ,  C07D233/38 ,  G01N33/54306 ,  G01N33/54353 ,  G01N33/552 ,  B01J2219/00608 ,  B01J2219/0061 ,  B01J2219/00612 ,  B01J2219/00617 ,  B01J2219/00626 ,  B01J2219/0063 ,  B01J2219/00659 ,  B01J2219/00722 ,  C40B40/06 ,  Y02P20/55

    摘要： Methods and compositions are described for immobilizing anti-ligands, such as antibodies or antigens, hormones or hormone receptors, oligonucleotides, and polysaccharides on surfaces of solid substrates for various uses. The methods provide surfaces covered with caged binding members which comprise protecting groups capable of being removed upon application of a suitable energy source. Spatially addressed irradiation of predefined regions on the surface permits immobilization of anti-ligands at the activated regions on the surface. Cycles of irradiation on different regions of the surface and immobilization of different anti-ligands allows formation of an immobilized matrix of anti-ligands at defined sites on the surface. The immobilized matrix of anti-ligands permits simultaneous screenings of a liquid sample for ligands having high affinities for certain anti-ligands of the matrix. A preferred embodiment of the invention involves attaching photoactivatable biotin derivatives to a surface. Photolytic activation of the biotin derivatives forms biotin analogs having strong binding affinity for avidin. Biotinylated anti-ligands can be immobilized on activated regions of the surface previously treated with avidin.

    摘要翻译： 描述了用于在固体底物的表面上固定抗配体如抗体或抗原，激素或激素受体，寡核苷酸和多糖的方法和组合物用于各种用途。 这些方法提供了覆盖有笼式结合构件的表面，其包括在施加合适的能量源时能够被去除的保护基团。 表面上预定区域的空间照射辐射允许在表面上的活化区域上固定抗配体。 表面不同区域的照射周期和不同抗配体的固定允许在表面上限定的位点形成固定的抗配体基团。 抗配体的固定化基质允许对基质的某些抗配体具有高亲和力的配体的液体样品的同时筛选。 本发明的优选实施方案涉及将可光活化的生物素衍生物连接到表面。 生物素衍生物的光解活化形成对抗生物素蛋白具有强结合亲和力的生物素类似物。 生物素化的抗配体可以固定在先前用抗生物素蛋白处理的表面的活化区上。

    Nucleic acid encoding the D.sub.2 /Ml chimeric receptor
    54.
    发明授权
    Nucleic acid encoding the D.sub.2 /Ml chimeric receptor 失效
    编码D2 / M1嵌合受体的核酸

    公开(公告)号：US5264565A

    公开(公告)日：1993-11-23

    申请号：US645029

    申请日：1991-01-22

    申请人： Bruce P. England ,  Ronald W. Barrett

    发明人： Bruce P. England ,  Ronald W. Barrett

    IPC分类号： C07K14/72 ,  C12P21/00 ,  C07H17/00 ,  C07K3/00 ,  C12N5/00

    CPC分类号： C07K14/723

    摘要： Chimeric G-protein linked receptors are constructed which retain ligand binding specificity yet gain the ability to elevate intracellular free calcium as a result of agonist binding. This easily assayed function is provided by the insertion of or replacement with sequences substantially homologous to the i3 loop of a second G-protein-linked receptor. Such receptors are employed, for example, in methods of screening for compounds capable of acting as agonists or antagonists of G-protein-linked receptors.

    摘要翻译： 构建了嵌合的G蛋白连接的受体，其保持配体结合特异性，但是由于激动剂结合而获得提升细胞内游离钙的能力。 通过插入或替换与第二G蛋白连接的受体的i3环基本上同源的序列来提供这种容易测定的功能。 这样的受体用于例如筛选能够作为G蛋白连接受体的激动剂或拮抗剂的化合物的方法。

    USE OF PRODRUGS OF GABA ANALOGS FOR TREATING DISEASES
    55.
    发明申请
    USE OF PRODRUGS OF GABA ANALOGS FOR TREATING DISEASES 审中-公开
    使用GABA类似物治疗疾病的原理

    公开(公告)号：US20120041061A1

    公开(公告)日：2012-02-16

    申请号：US13283469

    申请日：2011-10-27

    申请人： Ronald W. Barrett ,  Kenneth C. Cundy

    发明人： Ronald W. Barrett ,  Kenneth C. Cundy

    IPC分类号： A61K31/27 ,  A61P11/00 ,  A61P11/14 ,  A61P25/16 ,  A61P11/06

    CPC分类号： A61K31/195 ,  A61K31/197

    摘要： Methods of using prodrugs of GABA analogs and pharmaceutical compositions thereof to treat migraine, fibromyalgia, amyotrophic lateral sclerosis, irritable bowel syndrome, social phobia, Parkinson's disease, asthma, cough, or chronic obstructive pulmonary disease, and pharmaceutical compositions of prodrugs of GABA analogs useful in treating migraine, fibromyalgia, amyotrophic lateral sclerosis, irritable bowel syndrome, social phobia, Parkinson's disease, asthma, cough, or chronic obstructive pulmonary disease are disclosed.

    摘要翻译： 使用GABA类似物的前药及其药物组合物治疗偏头痛，纤维肌痛，肌萎缩性侧索硬化症，肠易激综合征，社交恐惧症，帕金森病，哮喘，咳嗽或慢性阻塞性肺疾病的药物组合物，以及GABA类似物的前药药物组合物 在治疗偏头痛，纤维肌痛，肌萎缩性侧索硬化症，肠易激综合征，社交恐惧症，帕金森病，哮喘，咳嗽或慢性阻塞性肺病方面。

    Method and apparatus for transferring and combining distinct chemical compositions with reagents
    57.
    发明授权
    Method and apparatus for transferring and combining distinct chemical compositions with reagents 失效
    用于将不同化学成分与试剂转移和组合的方法和装置

    公开(公告)号：US6054325A

    公开(公告)日：2000-04-25

    申请号：US887141

    申请日：1997-07-02

    申请人： Haim Kedar ,  Jeffrey H. Sugarman ,  Alastair A. Binnie ,  Ronald W. Barrett

    发明人： Haim Kedar ,  Jeffrey H. Sugarman ,  Alastair A. Binnie ,  Ronald W. Barrett

    IPC分类号： B01J19/00 ,  B01L3/00 ,  C40B60/14 ,  G01N33/00 ,  G01N21/00

    CPC分类号： B01L3/5025 ,  B01J19/0046 ,  B01L3/50255 ,  B01J2219/00315 ,  B01J2219/00317 ,  B01J2219/00319 ,  B01J2219/00369 ,  B01J2219/00421 ,  B01J2219/00468 ,  B01J2219/005 ,  B01J2219/00585 ,  B01J2219/00596 ,  B01L2200/021 ,  B01L2300/069 ,  B01L2300/0819 ,  B01L2300/0829 ,  B01L2400/0406 ,  B01L2400/0409 ,  B01L2400/0688 ,  C40B60/14 ,  Y10T436/143333 ,  Y10T436/255 ,  Y10T436/2575

    摘要： The invention provides exemplary systems, methods, and apparatus for distinctly allocating liquids containing chemical compositions or compounds to known locations in an organized manner so that assays may be performed on the compositions, or so that the chemical compositions may be combined with other distinct chemical compositions or reagents prior to evaluation. In one exemplary embodiment, the invention provides a fluid transfer system which comprises a donor member having a plurality of separate regions. At least some of the regions contain at least one chemical composition, with each chemical composition being distinct from any other chemical composition in the donor member. An acceptor member is also provided and includes a plurality of defined locations which are each adapted to receive a liquid medium. A transfer mechanism is provided to systematically transfer at least some of the chemical compositions from the donor member regions to at least some of the acceptor member locations such that the locale of each transferred chemical composition within the acceptor member is known. Further, each of the acceptor member locations has a volume that is less than about 500 .mu.l. In this way, a large number of acceptor member locations may be provided within a single system to efficiently transfer, in parallel fashion, large numbers of chemical compositions from the donor member to the acceptor member where evaluation or further processing of the chemical compositions may proceed.

    摘要翻译： 本发明提供了以有组织的方式将含有化学组成或化合物的液体明确分配到已知位置的示例性系统，方法和装置，以便可以对组合物进行测定，或使化学组合物可与其它不同的化学组成 或试剂。 在一个示例性实施例中，本发明提供了一种流体传输系统，其包括具有多个分离区域的施主构件。 至少一些区域含有至少一种化学组成，每种化学组成与供体构件中的任何其它化学组成不同。 还提供受体构件并且包括多个限定的位置，每个位置适于接收液体介质。 提供转移机制以系统地将至少一些化学组合物从供体构件区域转移到至少一些受体构件位置，使得受体构件内的每个转移的化学组成的位置是已知的。 此外，每个受体构件位置具有小于约500μl的体积。 以这种方式，可以在单个系统内提供大量的受体构件位置，以平行方式有效地从施主构件向受体构件传递大量的化学组成，其中化学组成的评估或进一步处理可以进行 。