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    Topologically segregated, encoded solid phase libraries comprising linkers having an enzymatically susceptible bond
    1.
    发明授权
    Topologically segregated, encoded solid phase libraries comprising linkers having an enzymatically susceptible bond 有权
    包含具有酶敏感键的接头的拓扑分离的编码固相文库

    公开(公告)号：US6090912A

    公开(公告)日：2000-07-18

    申请号：US198209

    申请日：1998-11-23

    申请人： Michal Lebl ,  Kit S. Lam ,  Sydney E. Salmon ,  Victor Krchnak ,  Nikolai Sepetov ,  Peter Kocis

    发明人： Michal Lebl ,  Kit S. Lam ,  Sydney E. Salmon ,  Victor Krchnak ,  Nikolai Sepetov ,  Peter Kocis

    IPC分类号： G01N33/53 ,  C07B61/00 ,  C07K1/04 ,  C07K17/00 ,  C40B70/00 ,  G01N33/543 ,  G01N33/566 ,  C07K4/00 ,  C07K1/00 ,  C12N9/48

    CPC分类号： C07K1/047 ,  B01J2219/00572 ,  B01J2219/00596 ,  C40B70/00

    摘要： The invention relates to libraries of synthetic test compound attached to separate phase synthesis supports. In particular, the invention relates to libraries of synthetic test compound attached to separate phase synthesis supports that also contain coding molecules that encode the structure of the synthetic test compound. The molecules may be polymers or multiple nonpolymeric molecules. Each of the solid phase synthesis support beads contains a single type of synthetic test compound. The synthetic test compound can have backbone structures with linkages such as amide, urea, carbamate (i.e., urethane), ester, amino, sulfide, disulfide, or carbon--carbon, such as alkane and alkene, or any combination thereof. Examples of subunits suited for the different linkage chemistries are provided. The synthetic test compound can also be molecular scaffolds, such as derivatives of monocyclic of bicyclic carbohydrates, steroids, sugars, heterocyclic structures, polyaromatic structures, or other structures capable of acting as a scaffolding. Examples of suitable molecular scaffolds are provided. The invention also relates to methods of synthesizing such libraries and the use of such libraries to identify and characterize molecules of interest from among the library of synthetic test compound.

    摘要翻译： 本发明涉及附着于分离相合成载体的合成试验化合物的文库。 特别地，本发明涉及连接到分离相合成载体上的合成测试化合物文库，其中还包含编码合成测试化合物结构的编码分子。 分子可以是聚合物或多个非聚合物分子。 每个固相合成载体珠含有单一类型的合成试验化合物。 合成试验化合物可以具有带有键合的主链结构，例如酰胺，脲，氨基甲酸酯（即氨基甲酸酯），酯，氨基，硫化物，二硫化物或碳 - 碳如烷烃和烯烃，或其任何组合。 提供了适用于不同连接化学物质的亚基的实例。 合成试验化合物还可以是分子支架，例如双环碳水化合物，类固醇，糖，杂环结构，多芳族结构或能够作为脚手架的其它结构的单环衍生物。 提供了合适的分子支架的实例。 本发明还涉及合成这些文库的方法，以及使用此类文库从合成测试化合物文库中鉴定和表征目标分子。

    Topologically segregated, encoded solid phase libraries
    2.
    发明授权
    Topologically segregated, encoded solid phase libraries 失效
    拓扑分离，编码固相库

    公开(公告)号：US5840485A

    公开(公告)日：1998-11-24

    申请号：US249830

    申请日：1994-05-26

    申请人： Michal Lebl ,  Kit S. Lam ,  Sydney E. Salmon ,  Victor Krchnak ,  Nikolai Sepetov ,  Peter Kocis

    发明人： Michal Lebl ,  Kit S. Lam ,  Sydney E. Salmon ,  Victor Krchnak ,  Nikolai Sepetov ,  Peter Kocis

    IPC分类号： C07K17/00 ,  C07K1/04 ,  C12P21/00 ,  C12Q1/00 ,  C40B70/00 ,  C12Q1/68 ,  C07H21/04 ,  C07K17/02 ,  G01N33/53

    CPC分类号： C07K1/047 ,  B01J2219/00572 ,  B01J2219/00596 ,  C40B70/00

    摘要： The invention relates to libraries of synthetic test compound attached to separate phase synthesis supports that also contain coding molecules that encode the structure of the synthetic test compound. The molecules may be polymers or multiple nonpolymeric molecules. The synthetic test compound can have backbone structures with linkages such as amide, urea, carbamate (i.e., urethane), ester, amino, sulfide, disulfide, or carbon-carbon, such as alkane and alkene, or any combination thereof. Examples of subunits suited for the different linkage chemistries are provided. The synthetic test compound can also be molecular scaffolds, such as derivatives of monocyclic of bicyclic carbohydrates, steroids, sugars, heterocyclic structures, polyaromatic structures, or other structures capable of acting as a scaffolding. Examples of suitable molecular scaffolds are provided. The invention also relates to methods of synthesizing such libraries and the use of such libraries to identify and characterize molecules of interest from among the library of synthetic test compound.

    摘要翻译： 本发明涉及连接到分离相合成载体上的合成试验化合物文库，其中还包含编码合成测试化合物结构的编码分子。 分子可以是聚合物或多个非聚合物分子。 合成试验化合物可以具有带有键合的主链结构，例如酰胺，脲，氨基甲酸酯（即氨基甲酸酯），酯，氨基，硫化物，二硫化物或碳 - 碳如烷烃和烯烃，或其任何组合。 提供了适用于不同连接化学物质的亚基的实例。 合成试验化合物还可以是分子支架，例如双环碳水化合物，类固醇，糖，杂环结构，多芳族结构或能够用作脚手架的其它结构的单环衍生物。 提供了合适的分子支架的实例。 本发明还涉及合成这些文库的方法，以及使用此类文库从合成测试化合物文库中鉴定和表征目标分子。

    Motif Libraries
    3.
    发明授权
    Motif Libraries 失效
    主题图书馆

    公开(公告)号：US5846841A

    公开(公告)日：1998-12-08

    申请号：US754878

    申请日：1996-11-22

    申请人： Nikolai Sepetov ,  Victor Krchnak ,  Michal Lebl

    发明人： Nikolai Sepetov ,  Victor Krchnak ,  Michal Lebl

    IPC分类号： B01J19/00 ,  C07K1/04 ,  C40B40/10 ,  G01N33/53

    CPC分类号： C07K1/047 ,  B01J19/0046 ,  B01J2219/005 ,  B01J2219/0059 ,  B01J2219/00592 ,  B01J2219/00596 ,  B01J2219/00725 ,  C40B40/10

    摘要： The invention concerns libraries of chemical compounds, that are useful in medicinal chemistry and related arts, their methods of manufacture and methods of their use. In one embodiment the individual chemical species of the library are synthesized aleatoricly, i.e, by a process involving chance. The chemical species of the library are used while attached to solid phase supports. The library differs from previously disclosed libraries that were intended to be screened while in solid phase in that each individual solid phase support or identifiable portion of a solid phase array displays many species of ligands, collectively termed a "set." The library is constructed so that each set contains a single invariant structure, common to all the species of ligands attached to the particular solid phase support, which is termed a "motif." The invention teaches that libraries of motifs can be employed advantageously compared to known libraries wherein a single species is present on each support.

    摘要翻译： 本发明涉及可用于药物化学和相关领域的化学化合物的文库，其制造方法及其使用方法。 在一个实施方案中，文库的各个化学物质合成，即通过涉及机会的方法合成。 文库的化学物质在固相支持时使用。 该文库不同于以前公开的在固相中被筛选的文库，因为固相阵列的每个单独的固相支持物或可识别的部分显示出许多种类的配体，统称为“组”。 该文库被构造成使得每个集合包含单个不变结构，对于连接到特定固相支持体的所有配体物种都是共同的，其被称为“基序”。 本发明教导了与已知的文库相比，可有利地使用基序库，其中单个物质存在于每个载体上。

    Peptide sequencing using mass spectrometry
    4.
    发明授权
    Peptide sequencing using mass spectrometry 失效
    使用质谱法进行肽测序

    公开(公告)号：US5470753A

    公开(公告)日：1995-11-28

    申请号：US68947

    申请日：1993-05-28

    申请人： Nikolai Sepetov ,  Olga Issakova ,  Viktor Krchnak ,  Michal Lebl

    发明人： Nikolai Sepetov ,  Olga Issakova ,  Viktor Krchnak ,  Michal Lebl

    IPC分类号： G01N33/68 ,  G01N33/00

    CPC分类号： G01N33/6848 ,  G01N33/6818 ,  Y10T436/24

    摘要： The present invention relates to methods for determining the amino acid composition, and more preferably the sequence, of a peptide using mass spectrometric techniques. The method is particularly useful for sequencing peptides isolated from natural sources or from libraries of peptides that have been prepared synthetically, and for peptides that are not amenable to Edman degradation sequencing. In one embodiment, the method for determining the amino acid composition or sequence of a peptide comprises determining the difference of the mass of the peptide from the mass of a deuterium-hydrogen exchanged peptide, and from this difference determining the number of exchangeable (labile) hydrogen atoms (protons). Candidate peptides having amino acid compositions or sequences that do not contain the observed number of exchangeable protons are eliminated. In another embodiment, synthesis of a portion of the peptides in a library of peptides is terminated after each coupling step, whereby a set of sequentially truncated fragments of each peptide is formed. Thus the sequence of the peptide can be determined by determining the difference in the molecular weight between each peptide or fragment thereof and the sequentially smaller fragment of the peptide.

    摘要翻译： 本发明涉及使用质谱技术测定肽的氨基酸组成，更优选地确定肽的序列的方法。 该方法对于从天然来源分离的肽或从已经合成制备的肽的文库以及不适合于Edman降解测序的肽测序肽特别有用。 在一个实施方案中，用于确定肽的氨基酸组成或序列的方法包括测定肽的质量与氘 - 氢交换的肽的质量的差异，以及从确定可交换（不稳定） 氢原子（质子）。 具有不含观察数量的可交换质子的氨基酸组成或序列的候选肽被消除。 在另一个实施方案中，在每个偶联步骤之后终止肽文库中肽的一部分的合成，由此形成每组肽的一系列顺序截短的片段。 因此，肽的序列可以通过确定每个肽或其片段与序列较小的肽片段之间的分子量的差异来确定。

    Selectively cleavabe linners based on iminodiacetic acid esters for solid phase peptide synthesis
    5.
    发明授权
    Selectively cleavabe linners based on iminodiacetic acid esters for solid phase peptide synthesis 失效
    用于固相肽合成的基于亚氨基二乙酸酯的选择性切割的接头

    公开(公告)号：US5635598A

    公开(公告)日：1997-06-03

    申请号：US263289

    申请日：1994-06-21

    申请人： Michal Lebl ,  Viktor Krchnak ,  Petr Kocis ,  Kit S. Lam

    发明人： Michal Lebl ,  Viktor Krchnak ,  Petr Kocis ,  Kit S. Lam

    IPC分类号： A61K38/00 ,  C07K5/00 ,  C07K1/04 ,  A61K38/02

    CPC分类号： C07K1/042

    摘要： The present invention is directed to linkers based on ester bond linkages, especially iminodiacetic acid ester bond linkages, for use in solid phase peptide synthesis. In particular, the invention is directed to cleavable linkers that can release peptide from the solid phase support under relatively mild conditions by formation of a diketopiperazine or other cyclic structure, such that the cyclic structure remains on the solid phase support, and, in a second cleavage, under more stringent conditions of high pH. The invention is further directed to solid phase supports prepared with multiple cleavable linkers, including a linker that is cleaved by formation of a cyclic product. One such second linker is an ester of hydroxymethylbenzoic acid, or esters formed by carboxy groups of aspartic or glutamic acid.

    摘要翻译： 本发明涉及用于固相肽合成的基于酯键连接的接头，特别是亚氨基二乙酸酯键键。 特别地，本发明涉及可切割的接头，其可以通过形成二酮哌嗪或其它环状结构在相对温和的条件下从固相支持物释放肽，使得环状结构保留在固相载体上，并且在第二 在更严格的高pH条件下开裂。 本发明还涉及用多个可切割接头制备的固相载体，其包括通过形成环状产物而被切割的连接体。 一个这样的第二接头是羟甲基苯甲酸的酯，或由天冬氨酸或谷氨酸的羧基形成的酯。

    Apparatus for fragmenting nucleic acids
    6.
    发明授权
    Apparatus for fragmenting nucleic acids 有权
    破碎核酸的装置

    公开(公告)号：US08597594B2

    公开(公告)日：2013-12-03

    申请号：US13551704

    申请日：2012-07-18

    申请人： Jonathan Posner ,  Kamil Salloum ,  Michal Lebl ,  Mark Reed ,  Dale Buermann ,  Matthew Hage ,  Bryan Crane ,  David Heiner ,  Robert Kain ,  Michael Schroeder

    发明人： Jonathan Posner ,  Kamil Salloum ,  Michal Lebl ,  Mark Reed ,  Dale Buermann ,  Matthew Hage ,  Bryan Crane ,  David Heiner ,  Robert Kain ,  Michael Schroeder

    IPC分类号： B01L3/00

    CPC分类号： F04B37/10 ,  F04B19/00 ,  Y10T436/2575

    摘要： An apparatus for fragmenting nucleic acid. The apparatus includes a sample reservoir that comprises a fluid having nucleic acids. The apparatus can also include a shear wall that is positioned within the sample reservoir. The shear wall includes a porous core medium that has pores that are sized to permit nucleic acids to flow therethrough. The apparatus also includes first and second chambers that are separated by the shear wall. The first and second chambers are in fluid communication with each other through the porous core medium of the shear wall. Also, the apparatus may include first and second electrodes that are located within the first and second chambers, respectively. The first and second electrodes are configured to generate an electric field that induces a flow of the sample fluid. The nucleic acids move through the shear wall thereby fragmenting the nucleic acids.

    摘要翻译： 核酸分裂装置。 该装置包括包含具有核酸的流体的样品储存器。 该装置还可以包括位于样品容器内的剪切壁。 剪切壁包括多孔芯介质，其具有尺寸允许核酸流过其中的孔。 该装置还包括被剪力墙隔开的第一和第二室。 第一和第二腔室通过剪切壁的多孔纤维介质彼此流体连通。 此外，该装置可以包括分别位于第一和第二室内的第一和第二电极。 第一和第二电极被配置成产生诱发样品流体流动的电场。 核酸通过剪切壁移动，从而使核酸分裂。