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    PEPTIDES USEFUL AS INTERNAL STANDARDS FOR MICROSEQUENCING AND METHODS FOR THEIR USE
    4.
    发明申请
    PEPTIDES USEFUL AS INTERNAL STANDARDS FOR MICROSEQUENCING AND METHODS FOR THEIR USE 审中-公开
    有用的微生物作为内部使用标准的方法及其使用方法

    公开(公告)号：WO1994002856A1

    公开(公告)日：1994-02-03

    申请号：PCT/US1993006932

    申请日：1993-07-23

    Applicant: THE UNITED STATES OF AMERICA, as represented by the SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

    Inventor： THE UNITED STATES OF AMERICA, as represented by the SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  PARMELEE, David, C. ,  SECHI, Salvatore

    IPC: G01N33/68

    CPC classification number: C07K14/4717 ,  C07K1/128 ,  C07K14/001 ,  G01N33/6824

    Abstract: The present invention provides a novel internal standard for amino acid sequencing which contains a peptide consisting of unnatural amino acid residues, such as ornithine, norvaline, norleucine and (alpha)-aminobutyric acid, that is capable of being sequenced simultaneously with an unknown peptide or protein without interfering with the analysis. The internal standard peptide has an amino acid sequence containing at least two different unnatural amino acid residues having retention times distinct from the corresponding retention times for natural amino acid residues. Information derived from the sequencing of the internal standard allows determination of repetitive yield, lag, N-terminal blockage and discrimination between blank cycles caused by missed injection and blank cycles caused by faulty delivery of chemicals during the sequencer reactions. The present invention further provides novel synthetic control peptides containing from about 3 to 100 natural amino acid residues that are designed for use in monitoring the proper operation of amino acid sequencers and to monitor peptide or protein cleavage reactions. The control peptide, or mixture of control peptides, are designed to obtain data for many or all common, uncommon and difficult to measure amino acids within 15 sequencer cycles and to provide cleavage sites for at least 4 different amino acide cleavage reactants.

    Abstract translation: 本发明提供了用于氨基酸测序的新型内标，其包含由非天然氨基酸残基组成的肽，例如鸟氨酸，正缬氨酸，正亮氨酸和（α） - 氨基丁酸，其能够与未知肽同时测序或 蛋白质而不干扰分析。 内标肽具有含有至少两个不同的天然氨基酸残基的氨基酸序列，其保留时间与天然氨基酸残基的相应保留时间不同。 从内标测序获得的信息可以确定重复产量，滞后，N末端阻塞以及在排序反应期间由错误输送化学品导致的错过注射和空白循环引起的空白循环之间的差异。 本发明还提供了含有约3至100个天然氨基酸残基的新型合成对照肽，其被设计用于监测氨基酸测序仪的正常操作并监测肽或蛋白质切割反应。 设计对照肽或对照肽的混合物以在15个测序仪周期内获得许多或所有常见的，不常见的和难以测量的氨基酸的数据，并为至少4种不同的氨基酸切割反应物提供切割位点。

    METHOD OF FORMING N-PROTECTED AMINO ACID THIOHYDANTOINS
    5.
    发明申请
    METHOD OF FORMING N-PROTECTED AMINO ACID THIOHYDANTOINS 审中-公开
    形成N-保护氨基酸乙醇酸的方法

    公开(公告)号：WO1994002468A1

    公开(公告)日：1994-02-03

    申请号：PCT/US1993006625

    申请日：1993-07-14

    Applicant: APPLIED BIOSYSTEMS, INC.

    Inventor： APPLIED BIOSYSTEMS, INC. ,  BOYD, Victoria, L. ,  BOZZINI, MeriLisa ,  GUGA, Piotr, J. ,  ZON, Gerold

    IPC: C07D233/86

    CPC classification number: C07D233/86 ,  C07K1/128 ,  G01N33/6821 ,  Y02P20/55 ,  Y10S366/03

    Abstract: A method of forming a thiohydantoin of formula (II) from an N-protected amino acid (I) is described. The method employs a uronium (III) or phosphonium (IV) compound to activate the terminal carboxyl group of the amino acid and a thiocyanate reagent to cyclize the activated amino acid to the thiohydantoin. The thiohydantoin can be cleaved from its N-protecting group, for use in C-terminal peptide sequencing. Particularly preferred uronium compounds include salts of 2-chlorouronium. Preferred thiocyanate reagents include trimethylsilyl isothiocyanate and crown ether adducts of metallothiocyanates, such as the 18-crown-6 adduct of KSCN.

    Abstract translation: 描述了由N-保护的氨基酸（I）形成式（II）的硫代乙内酰脲的方法。 该方法采用脲（III）或鏻（Ⅳ）化合物来活化氨基酸的末端羧基和硫氰酸酯试剂，将活化的氨基酸环化成硫代乙内酰脲。 硫代乙内酰脲可以从其N-保护基裂解，用于C末端肽测序。 特别优选的尿素化合物包括2-氯脲的盐。 优选的硫氰酸酯试剂包括异硫氰酸三甲基甲硅烷基酯和金属硫氰酸酯的冠醚加合物，例如KSCN的18-冠-6加合物。

    PIEZOELECTRIC FORCE SENSING APPARATUS AND METHODS FOR BIOPOLYMER SEQUENCING
    9.
    发明申请
    PIEZOELECTRIC FORCE SENSING APPARATUS AND METHODS FOR BIOPOLYMER SEQUENCING 审中-公开
    压电力传感装置和生物聚合物测序方法

    公开(公告)号：WO1997016699A1

    公开(公告)日：1997-05-09

    申请号：PCT/US1996014462

    申请日：1996-09-10

    Applicant: TRUSTEES OF BOSTON UNIVERSITY

    Inventor： TRUSTEES OF BOSTON UNIVERSITY ,  CANTOR, Charles, R. ,  SMITS, Johannes, G. ,  SMITH, Cassandra, L.

    IPC: G01B07/34

    CPC classification number: C07K1/128 ,  B82Y35/00 ,  C12Q1/68 ,  C12Q1/6869 ,  C12Q2565/607

    Abstract: The invention relates to methods and apparatus for determining the structure of a biopolymer by piezoelectric force sensing. Biopolymers which can be analyzed include nucleic acids, proteins, polysaccharides and most any sequence of monomers. Biopolymers or biopolymer fragments are attached to a force sensing apparatus and subjected to an electric or magnetic field. The target generates a detectable force on the force sensing apparatus. Force information collected from multiple force sensing elements can be compiled and the structure of the biopolymer determined. Structure information determined may reveal sequence, size, mass or charge information specific for the biopolymer. The invention also relates to methods for the detection of biopolymers in a heterogenous mixture and methods for the detection of a disorder by piezoelectric force sensing. The invention further relates to methods and devices for measuring the mass of a molecular or macromolecular target by analyzing harmonic resonance frequencies.

    Abstract translation: 本发明涉及通过压电力感测来确定生物聚合物的结构的方法和装置。 可以分析的生物聚合物包括核酸，蛋白质，多糖和大多数任何单体序列。 生物聚合物或生物聚合物碎片连接到力感测装置并经受电场或磁场。 目标在力感测装置上产生可检测力。 可以编制从多个力传感元件收集的力信息，并确定生物聚合物的结构。 确定的结构信息可能会显示生物聚合物特有的序列，大小，质量或电荷信息。 本发明还涉及用于检测异种混合物中的生物聚合物的方法和通过压电力感测来检测病症的方法。 本发明还涉及通过分析谐波谐振频率来测量分子或大分子靶的质量的方法和装置。

    METHODS AND APPARATUS FOR SEQUENCING POLYMERS WITH A STATISTICAL CERTAINTY USING MASS SPECTROMETRY
    10.
    发明申请
    METHODS AND APPARATUS FOR SEQUENCING POLYMERS WITH A STATISTICAL CERTAINTY USING MASS SPECTROMETRY 审中-公开
    使用大规模光谱测定具有统计特征的聚合物的方法和装置

    公开(公告)号：WO1996036986A1

    公开(公告)日：1996-11-21

    申请号：PCT/US1996007146

    申请日：1996-05-17

    Applicant: PERSEPTIVE BIOSYSTEMS, INC.

    Inventor： PERSEPTIVE BIOSYSTEMS, INC. ,  PATTERSON, Dale, H. ,  TARR, George, E.

    IPC: H01J49/04

    CPC classification number: G01N33/6848 ,  C07K1/128 ,  C12P21/06 ,  C12Q1/34 ,  H01J49/0036

    Abstract: The method and apparatus disclosed herein are useful for sequencing polymers using mass spectrometry. The methods involve differing ratios of hydrolyzing agent to polymer disposed upon a reaction surface adapted for use with a mass spectrometer. The methods further involve integrating data obtained from mass spectrometry analysis of a plurality of series of hydrolyzed polymer fragments, and provide statistical interpretation paradigms and computer software therefor. The apparatus involves a mass spectrometer sample holder, having hydrolyzing agent disposed thereon, which is useful for adapting any mass spectrometer for polymer sequencing.

    Abstract translation: 本文公开的方法和装置可用于使用质谱法测序聚合物。 该方法涉及不同比例的水解剂与聚合物的配置在适合与质谱仪一起使用的反应表面上。 该方法进一步包括从多个水解聚合物片段系列的质谱分析中获得的数据，并提供统计解释范例及其计算机软件。 该装置包括质谱仪样品架，其上设置有水解剂，其可用于使任何质谱仪适合聚合物测序。

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