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公开(公告)号：US06664058B2
公开(公告)日：2003-12-16
申请号：US09898210
申请日：2001-07-03
申请人： Shiv Kumar , Satyam Nampalli , Constantin Neagu , Mark McDougall , David Loakes , Dan Brown
发明人： Shiv Kumar , Satyam Nampalli , Constantin Neagu , Mark McDougall , David Loakes , Dan Brown
IPC分类号： C12Q168
CPC分类号： C07D487/04 , C07F9/6561 , C07H19/23 , C12Q2525/117 , G01N33/58
摘要： The present invention describes novel compounds of the formula Wherein Q is H or a sugar or a sugar analogue or a nucleic acid backbone or backbone analogue, Y=O, S, NR10, where R10 is H, alkyl alkenyl, alkynyl, X is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl or a combination thereof or, preferably, a reporter group. The novel compounds are suitable for incorporation in oligonucleotides and polynucleotides.
摘要翻译： 本发明描述了新颖的式化合物，其中Q是H或糖或糖类似物或核酸主链或主链类似物，Y = O，S，NR 10，其中R 10是H，烷基烯基， 炔基，X是H，烷基，烯基，炔基，芳基，杂芳基或其组合，或优选报道基团。 新型化合物适用于掺入寡核苷酸和多核苷酸。
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公开(公告)号：US06600028B1
公开(公告)日：2003-07-29
申请号：US09402048
申请日：2000-02-01
申请人： Daniel Brown , David Loakes , David Williams , Fergal Hill , Shiv Kumar , Satyam Nampalli , Mark McDougall , Alan Hamilton , Clifford Smith , Adrian Christopher Simmonds , William Jonathan Cummins , Patrick Finn
发明人： Daniel Brown , David Loakes , David Williams , Fergal Hill , Shiv Kumar , Satyam Nampalli , Mark McDougall , Alan Hamilton , Clifford Smith , Adrian Christopher Simmonds , William Jonathan Cummins , Patrick Finn
IPC分类号： C07H2100
CPC分类号： C07D498/16 , C07H19/04 , C07H21/00
摘要： Nucleoside analogues have structure (2) wherein Q is H or a sugar moiety or sugar analogue or a modified sugar or a nucleic backbone or backbone analogue, W is an alkylene or alkenylene chain of 0-5 carbon atoms, any of which may carry a substituent R8, X is O or N or NR12 or CR10, X′ is O or S or N, provided that when X′ is O or S, then X is C, Y is CH or N, R6 is NH2 or SMe or SO2Me or NHNH2, each of R7 and R8 is independently H or F or alkyl or alkenyl or aryl or acyl or a reporter moiety, R12 is independently H or alkyl or alkenyl or aryl or acyl or a reporter moiety, and R10 is H or ═O or F or alkyl or aryl or a reporter moiety.
摘要翻译： 核苷类似物具有结构（2），其中Q是H或糖部分或糖类似物或修饰的糖或核心或骨架类似物，W是0-5个碳原子的亚烷基或亚烯基链，其中任何一个可携带 取代基R8，X为O或N或NR12或CR10，X'为O或S或N，条件是当X'为O或S时，则X为C，Y为CH或N，R6为NH2或SMe或SO2Me 或NHNH 2，R 7和R 8各自独立地为H或F，或烷基或链烯基或芳基或酰基或报道部分，R 12独立地为H或烷基或链烯基或芳基或酰基或报道部分，R 10为H或= O 或F或烷基或芳基或报道部分。
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公开(公告)号：US06444682B1
公开(公告)日：2002-09-03
申请号：US09463501
申请日：2000-04-18
申请人： Adrian Christopher Simmonds , Alan Hamilton , Clifford Smith , David Loakes , Daniel Brown , Fergal Hill , Shiv Kumar , Satyam Nampalli , Mark McDougall
发明人： Adrian Christopher Simmonds , Alan Hamilton , Clifford Smith , David Loakes , Daniel Brown , Fergal Hill , Shiv Kumar , Satyam Nampalli , Mark McDougall
IPC分类号： A61K3170
CPC分类号： G01N33/5308 , C07H21/00
摘要： Nucleotide or base analogues having structure (3) or (4) wherein X═O or NH or S and each R6 is independently H or alkyl or alkenyl or alkoxy or aryl or a reporter moiety.
摘要翻译： 具有结构（3）或（4）的核苷酸或碱基类似物，其中X = O或NH或S，每个R6独立地为H或烷基或链烯基，烷氧基或芳基或报道部分。
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公开(公告)号：US06605611B2
公开(公告)日：2003-08-12
申请号：US10233993
申请日：2002-09-03
申请人： Adrian Christopher Simmonds , Alan Hamilton , Clifford Smith , David Loakes , Daniel Brown , Fergal Hill , Shiv Kumar , Satyam Nampalli , Mark McDougall
发明人： Adrian Christopher Simmonds , Alan Hamilton , Clifford Smith , David Loakes , Daniel Brown , Fergal Hill , Shiv Kumar , Satyam Nampalli , Mark McDougall
IPC分类号： A61K31495
CPC分类号： G01N33/5308 , C07H21/00
摘要： Nucleoside analogues or base analogues having structure (I), where X=O or NH or S, Y=N or CHR6 or CR6, W=N or NR6 or CHR6 or CR6 or S, n=1 or 2; each R6 is independently H or O or alkyl or alkenyl or alkoxy or aryl or a reporter moiety; where necessary (i.e. when Y and/or W is N or CR6 where R6 is not O) a double bond is present between Y and W or W and W, and Q is H or a sugar or a sugar analogue or a nucleic acid backbone or backbone analogue.
摘要翻译： 具有结构（I）的核苷类似物或碱基类似物，其中X = O或NH或S，Y = N或CHR 6或CR 6，W = N或NR 6或CHR 6或CR 6或S，n = 1或2; 每个R 6独立地为H或O或烷基或链烯基或烷氧基或芳基或报道部分; 必要时（即当Y和/或W为N或R6，R6不为O时），Y与W或W和W之间存在双键，Q为H或糖或糖类似物或核酸骨架 或骨架类似物。
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公开(公告)号：US08778844B2
公开(公告)日：2014-07-15
申请号：US13147257
申请日：2010-02-04
IPC分类号： C40B30/04
CPC分类号： C12N15/1037 , A61K47/55 , A61K47/64 , A61K47/643 , C07K14/001 , C12N15/1044 , C12N15/1058 , C40B40/08 , C40B40/10 , C40B50/06 , G01N33/531
摘要： The invention relates to a method for modifying one or more peptide ligands, comprising polypeptides covalently linked to a molecular scaffold at two or more amino acid residues, comprising the steps of providing one or more peptide ligands, wherein the polypeptide comprises two or more reactive groups which form a covalent linkage to the molecular scaffold, and at least one loop which comprises a sequence of two or more amino acids subtended between two of said reactive groups; exposing the peptide ligands to one or more proteases; and sorting the ligands according to the extent of proteolytic cleavage.
摘要翻译： 本发明涉及一种修饰一种或多种肽配体的方法，其包括在两个或更多个氨基酸残基处与分子支架共价连接的多肽，包括提供一个或多个肽配体的步骤，其中所述多肽包含两个或多个反应性基团 其形成与分子支架的共价键，以及至少一个环，其包含在两个所述反应性基团之间对位的两个或更多个氨基酸的序列; 将肽配体暴露于一种或多种蛋白酶; 并根据蛋白水解切割的程度对配体进行分选。
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公开(公告)号：US20120142541A1
公开(公告)日：2012-06-07
申请号：US13147257
申请日：2010-02-04
CPC分类号： C12N15/1037 , A61K47/55 , A61K47/64 , A61K47/643 , C07K14/001 , C12N15/1044 , C12N15/1058 , C40B40/08 , C40B40/10 , C40B50/06 , G01N33/531
摘要： The invention relates to a method for modifying one or more peptide ligands, comprising polypeptides covalently linked to a molecular scaffold at two or more amino acid residues, comprising the steps of providing one or more peptide ligands, wherein the polypeptide comprises two or more reactive groups which form a covalent linkage to the molecular scaffold, and at least one loop which comprises a sequence of two or more amino acids subtended between two of said reactive groups; exposing the peptide ligands to one or more proteases; and sorting the ligands according to the extent of proteolytic cleavage.
摘要翻译： 本发明涉及一种修饰一种或多种肽配体的方法，其包括在两个或更多个氨基酸残基处与分子支架共价连接的多肽，包括提供一个或多个肽配体的步骤，其中所述多肽包含两个或多个反应性基团 其形成与分子支架的共价键，以及至少一个环，其包含在两个所述反应性基团之间对位的两个或更多个氨基酸的序列; 将肽配体暴露于一种或多种蛋白酶; 并根据蛋白水解切割的程度对配体进行分选。
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公开(公告)号：US20120101256A1
公开(公告)日：2012-04-26
申请号：US13147289
申请日：2010-02-04
申请人： Gregory Paul Winter , Christian Heinis , Elise Bernard , David Loakes , John Tite , Marina Vaysburd , Daniel Paul Teufel , Lutz Riechmann
发明人： Gregory Paul Winter , Christian Heinis , Elise Bernard , David Loakes , John Tite , Marina Vaysburd , Daniel Paul Teufel , Lutz Riechmann
CPC分类号： C12N15/1037 , A61K47/55 , A61K47/64 , A61K47/643 , C07K14/001 , C12N15/1044 , C12N15/1058 , C40B40/08 , C40B40/10 , C40B50/06 , G01N33/531
摘要： The invention relates to a method for providing a multispecific peptide ligand comprising a polypeptide covalently linked to a molecular scaffold at three or more amino acid residues and capable of binding to two or more separate targets, comprising the steps of: (a) providing a first repertoire of polypeptides, each polypeptide comprising two or more reactive groups capable of covalent linkage to a molecular scaffold, and at least one loop which comprises a sequence of two or more amino acids subtended between two of said reactive groups; (b) providing a second repertoire of polypeptides as described in (a); (c) joining at least one loop of one or more members of the first repertoire to at least one loop of one or more members of the second repertoire to form at least one polypeptide comprising two loops, and (d) conjugating the composite polypeptide(s) to a molecular scaffold at at least three amino acid positions.
摘要翻译： 本发明涉及一种提供多特异性肽配体的方法，所述多特异性肽配体包含在三个或更多个氨基酸残基处共价连接到分子支架并能够结合两个或更多个单独靶标的多肽，包括以下步骤：（a）提供第一 多肽的所有组成部分，每个多肽包含两个或更多个能够与分子支架共价连接的反应性基团，以及至少一个环，其包含两个或更多个氨基酸的序列，对应于两个所述反应性基团; （b）提供如（a）所述的第二组多肽; （c）将第一组合物中的一个或多个成员的至少一个环连接到第二组合物的一个或多个成员的至少一个环，以形成至少一个包含两个环的多肽，和（d）将复合多肽（ s）至少在三个氨基酸位置分子支架。
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公开(公告)号：US06239159B1
公开(公告)日：2001-05-29
申请号：US09101978
申请日：1999-05-03
申请人： Daniel Brown , David Loakes , Alan Hamilton , Adrian Simmonds , Clifford Smith
发明人： Daniel Brown , David Loakes , Alan Hamilton , Adrian Simmonds , Clifford Smith
IPC分类号： A01N4352
CPC分类号： C07H21/00 , C07H19/044 , C07H19/052 , C07H19/056
摘要： Nucleoside analogues in which a group M replaces the natural base where M is (1) or (2) or (3), where each of X1, X2 and X3 are C or N, each of R6 and R7 is the same or different and each is H, NO2, CO, COR8, OR8, CN, O, CON(R8)2, COOR8, SO2R8, SO3R8, SR8, NHCHO, (CH2)n(R8)2, halogen, or a reporter moiety, each of R8 and R9 is H or hydrocarbyl or a reporter moiety, and n is 0-4. The analogues are substrates for polymerase and terminal transferase enzymes.
摘要翻译： 其中M代替M为（1）或（2）或（3）的天然碱的核苷类似物，其中X1，X2和X3各自为C或N，R6和R7各自相同或不同， 各自为H，NO 2，CO，COR 8，OR 8，CN，O，CON（R 8）2，COOR 8，SO 2 R 8，SO 3 R 8，SR 8，NHCHO，（CH 2）n（R 8）2，卤素或报道分子 R8和R9是H或烃基或报道部分，n是0-4。 类似物是聚合酶和末端转移酶的底物。
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公开(公告)号：US09518081B2
公开(公告)日：2016-12-13
申请号：US13390252
申请日：2010-08-12
CPC分类号： C12N15/1037 , C07K1/00 , C07K1/042 , C07K1/113 , C07K2318/00
摘要： The invention relates to a method for altering the conformational diversity of a first repertoire of polypeptide ligands, comprising a plurality of polypeptides comprising at least two reactive groups separated by a loop sequence covalently linked to a molecular scaffold which forms covalent bonds with said reactive groups, to produce a second repertoire of polypeptide ligands, comprising assembling said second repertoire from the polypeptides and structural scaffold of said first repertoire, incorporating one of the following alterations: (a) altering at least one reactive group; or (b) altering the nature of the molecular scaffold; or (c) altering the bond between at least one reactive group and the molecular scaffold; or (d) any combination of (a), (b) or (c).
摘要翻译： 本发明涉及一种用于改变多肽配体的第一组分的构象多样性的方法，其包含多个多肽，所述多肽包含至少两个反应性基团，所述反应基团通过共价连接到与所述反应性基团形成共价键的分子支架的环序列分开， 以产生多肽配体的第二组成成分，其包括从所述第一组合物的多肽和结构性支架组装所述第二组分，并结合以下改变之一：（a）改变至少一个反应性基团; 或（b）改变分子支架的性质; 或（c）改变至少一个反应性基团和分子支架之间的键; 或（d）（a），（b）或（c）的任何组合。
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公开(公告)号：US20120172235A1
公开(公告)日：2012-07-05
申请号：US13390252
申请日：2010-08-12
CPC分类号： C12N15/1037 , C07K1/00 , C07K1/042 , C07K1/113 , C07K2318/00
摘要： The invention relates to a method for altering the conformational diversity of a first repertoire of polypeptide ligands, comprising a plurality of polypeptides comprising at least two reactive groups separated by a loop sequence covalently linked to a molecular scaffold which forms covalent bonds with said reactive groups, to produce a second repertoire of polypeptide ligands, comprising assembling said second repertoire from the polypeptides and structural scaffold of said first repertoire, incorporating one of the following alterations: (a) altering at least one reactive group; or (b) altering the nature of the molecular scaffold; or (c) altering the bond between at least one reactive group and the molecular scaffold; or (d) any combination of (a), (b) or (c).
摘要翻译： 本发明涉及一种用于改变多肽配体的第一组分的构象多样性的方法，其包含多个多肽，所述多肽包含至少两个反应性基团，所述反应基团通过共价连接到与所述反应性基团形成共价键的分子支架的环序列分开， 以产生多肽配体的第二组成成分，其包括从所述第一组合物的多肽和结构性支架组装所述第二组分，并结合以下改变之一：（a）改变至少一个反应性基团; 或（b）改变分子支架的性质; 或（c）改变至少一个反应性基团和分子支架之间的键; 或（d）（a），（b）或（c）的任何组合。
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