公开(公告)号：US20060022129A1

公开(公告)日：2006-02-02

申请号：US11136436

申请日：2005-05-25

申请人： Mikhail Shchepinov ,  Susan Wheeler ,  Edwin Southern

发明人： Mikhail Shchepinov ,  Susan Wheeler ,  Edwin Southern

IPC分类号： B01D59/44

CPC分类号： G01N33/6851 ,  G01N33/6848 ,  G01N2458/15

摘要： Methods of analysing peptides by mass spectrometry are disclosed. In particular, methods of analysing peptides by fragmentation mass spectrometry (MSn, where n is at least 2) are disclosed. The methods involve derivatisation of a peptide at its N-terminus such that peaks corresponding to both a and b (and y) daughter ions are identifiable in fragmentation mass spectra of the derivatised peptide. The fragmentation mass spectra of the derivatised peptide contain additional information (relative to the fragmentation mass spectra of the underivatised peptide) useful for determination of the amino acid sequence of the peptide.

摘要翻译： 公开了通过质谱分析肽的方法。 特别地，公开了通过碎片质谱法（MS＆lt; n＆gt;，其中n至少为2）分析肽的方法。 所述方法涉及在其N末端衍生肽，使得对应于a和b（和y）子离子的峰可在衍生肽的断裂质谱中鉴定。 衍生肽的断裂质谱包含可用于测定肽的氨基酸序列的附加信息（相对于未衍生肽的断裂质谱）。

公开(公告)号：US20050043414A1

公开(公告)日：2005-02-24

申请号：US10937545

申请日：2004-09-08

申请人： Mikhail Shchepinov ,  Edwin Southern

发明人： Mikhail Shchepinov ,  Edwin Southern

IPC分类号： G01N21/64 ,  C07C235/42 ,  C07H21/00 ,  C09B3/14 ,  C09B11/06 ,  C09K11/06 ,  C12Q1/68 ,  G01N21/78 ,  G01N33/50 ,  G01N33/53 ,  G01N33/533 ,  G01N33/542 ,  G01N33/58 ,  A61K31/495 ,  A61K31/03

CPC分类号： C07H21/00 ,  C09B3/14 ,  C09B11/06 ,  G01N33/542

摘要： The present invention pertains to trityl-type compounds comprising, bonded to the same atom, three aryl groups, of which at least one is a fluorophore and at least one has a substituent including a functional group, and wherein the compound can exist in a non-ionised state or in an ionised state conjugated with the aryl groups.

摘要翻译： 本发明涉及三苯甲基型化合物，其包含与相同原子键合的三个芳基，其中至少一个是荧光团，至少一个具有包含官能团的取代基，并且其中该化合物可以以非 - 或与芳基共轭的电离状态。

公开(公告)号：US20050003408A1

公开(公告)日：2005-01-06

申请号：US10843873

申请日：2004-05-11

申请人： Edwin Southern ,  Mikhail Shchepinov ,  John Housby ,  Alan Hamilton ,  John Elder

发明人： Edwin Southern ,  Mikhail Shchepinov ,  John Housby ,  Alan Hamilton ,  John Elder

IPC分类号： G01N27/62 ,  C07B61/00 ,  C07H21/00 ,  C12M1/00 ,  C12N15/09 ,  C12Q1/68 ,  C40B20/04 ,  C40B30/04 ,  C40B30/10 ,  C40B40/06 ,  C40B40/10 ,  C40B50/10 ,  C40B60/10 ,  C40B70/00 ,  G01N33/483 ,  G01N33/50 ,  C12P19/34

CPC分类号： C12Q1/6872 ,  C07H21/00 ,  C40B20/04 ,  C40B30/04 ,  C40B30/10 ,  C40B40/06 ,  C40B40/10 ,  C40B50/10 ,  C40B50/16 ,  C40B60/10 ,  C40B70/00

摘要： A method of making a set of labelled compounds by the use of a preferably particulate support, comprises dividing the support into lots, performing a different chemical reaction on each lot of the support, e.g. to couple a chemical moiety to that lot of the support, tagging a fraction of each lot of the support with a different label, and combining the said lots of the support. The steps are repeated several times, preferably to build up oligomer molecules carrying labels which identify the nature and position of a monomer unit of the oligomer, and which are releasable from the support. Preferred labels, which are releasable from the compounds by cleavage to provide charged groups for analysis by mass spectrometry, are groups of the trityl (trimethylphenyl) family. Also claimed are libraries of these labels is and their use in assays and nucleic acid analysis methods.

摘要翻译： 通过使用优选颗粒载体制备一组标记化合物的方法包括将载体分成批次，在每批载体上进行不同的化学反应。 将化学部分连接到许多支持物，用不同的标签标记每批支持物的一小部分，并且组合所述许多支持物。 重复这些步骤数次，优选地构建携带标记物的标签的低聚物分子，其标识低聚物的单体单元的性质和位置，并且其可从载体上释放。 优选的标记物，可通过裂解从化合物中释放以提供用于通过质谱分析的带电基团，是三苯甲基（三甲基苯基）家族的组。 还要求保护的是这些标记的文库是它们在测定和核酸分析方法中的用途。

公开(公告)号：US20110065196A1

公开(公告)日：2011-03-17

申请号：US11922235

申请日：2006-06-16

申请人： Mikhail Shchepinov ,  Pablo Bernad

发明人： Mikhail Shchepinov ,  Pablo Bernad

IPC分类号： G01N33/50 ,  C07K1/13 ,  C07C43/205 ,  C07C323/16 ,  C07C323/60 ,  C07C235/34 ,  C07H1/00 ,  C07H21/04

CPC分类号： C07C323/60 ,  C07C323/16 ,  C07D207/46 ,  C07F7/12 ,  C07H21/00 ,  G01N33/6848 ,  Y10T436/143333 ,  Y10T436/17 ,  Y10T436/182 ,  Y10T436/200833

摘要： The present invention provides a method of forming an ion of formula (I) comprising the steps of: (i) reacting a compound of the formula (IIa); with a biopolymer, BP, having at least one group capable of reacting with M to form a covalent linkage, to provide a biopolymer derivative of the formula (IIIa); and (ii) cleaving the C—X bond between X and the α-carbon atom of the derivative of formula (IIIa) to form the ion of formula (I); where: (IV) is a carbon atom bearing a single positive charge or a single negative charge; and X is a group comprising a thioether sulphur atom bound directly to the α-carbon which is capable of being cleaved from the α-carbon atom to form an ion of formula (I). The biopolymer derivatives of the invention have enhanced ionisability with respect to free biopolymer (BP) enabling improved analysis of the biopolymer using mass spectrometry.

摘要翻译： 本发明提供形成式（I）离子的方法，包括以下步骤：（i）使式（IIa）化合物与式 具有至少一个能够与M反应以形成共价键的生物聚合物BP，以提供式（IIIa）的生物聚合物衍生物; 和（ii）裂解X与式（IIIa）的衍生物的α-碳原子之间的C-X键以形成式（I）的离子; 其中：（IV）是具有单个正电荷或单个负电荷的碳原子; X是包含直接与α-碳结合的硫醚硫原子的基团，其能够从α-碳原子切割而形成式（I）的离子。 本发明的生物聚合物衍生物相对于游离生物聚合物（BP）具有增强的电离性，能够使用质谱法改进对生物聚合物的分析。

公开(公告)号：US20070219367A1

公开(公告)日：2007-09-20

申请号：US10574130

申请日：2004-10-20

申请人： Mikhail Shchepinov ,  Kalim Mir

发明人： Mikhail Shchepinov ,  Kalim Mir

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6874 ,  C12Q1/6818 ,  C12Q1/6869 ,  G01N21/6428 ,  G01N2021/6432 ,  G01N2021/6441 ,  C12Q2565/501 ,  C12Q2565/101 ,  C12Q2563/155 ,  C12Q2565/518 ,  C12Q2533/107 ,  C12Q2535/122 ,  C12Q2533/101 ,  C12Q2563/173 ,  C12Q2565/301 ,  C12Q2561/113

摘要： The present invention relates to a method of sequencing a target polynucleotide by enzymatic and/or chemical means. The sequencing method includes a method for characterizing multiple alleles in a sample, a method of calculating confidence levels in ascertained sequences, a method for comparing polynucleotide sequences, and a method of resolving ambiguities in a polynucleotide sequence. It also provides methods for appropriately preparing samples, for immobilizing template molecules, for organizing the template molecules, and to conduct the sequencing of many molecules in parallel. The method involves analyzing molecules as members of an array. Many target polynucleotides or many segments of a single target polynucleotide can be sequenced simultaneously. In a preferred embodiment, the method involves analyzing individual molecules within an array and base calls are based on the signals from two or more molecules. A method to prevent non-specific signal in sequencing is also provided. The invention is readily automated, both for small-scale and large-scale operation and relevant algorithms and the composition of kits and systems are provided.

摘要翻译： 本发明涉及通过酶和/或化学方法测序靶多核苷酸的方法。 测序方法包括用于表征样品中的多个等位基因的方法，计算确定的序列中的置信水平的方法，比较多核苷酸序列的方法和解决多核苷酸序列中的模糊度的方法。 它还提供适当制备样品，固定模板分子，组织模板分子以及并行进行许多分子测序的方法。 该方法包括分析分子作为阵列的成员。 单个靶多核苷酸的许多靶多核苷酸或许多片段可以同时测序。 在优选的实施方案中，该方法包括分析阵列内的各个分子，并且基于来自两个或更多个分子的信号进行碱基呼叫。 还提供了一种在排序中防止非特异性信号的方法。 本发明容易地自动化，用于小规模和大规模操作以及相关算法，并提供了套件和系统的组成。