公开(公告)号：US07579165B2

公开(公告)日：2009-08-25

申请号：US10962575

申请日：2004-10-13

申请人： Shigemi Norioka ,  Minoru Yamaguchi ,  Hiroki Kuyama ,  Takashi Obama ,  Eiji Ando ,  Takashi Nakazawa ,  Norikazu Ueyama ,  Taka-aki Okamura

发明人： Shigemi Norioka ,  Minoru Yamaguchi ,  Hiroki Kuyama ,  Takashi Obama ,  Eiji Ando ,  Takashi Nakazawa ,  Norikazu Ueyama ,  Taka-aki Okamura

IPC分类号： C07K1/13 ,  C07K1/14 ,  C07K14/00 ,  C12P21/06 ,  C12Q1/00 ,  C12Q1/34 ,  C12Q1/37 ,  G01N33/53 ,  G01N33/38 ,  G01N33/483

CPC分类号： C12N9/2462 ,  C07K1/1077 ,  C07K1/128 ,  C07K14/78

摘要： The present invention provides a method for effectively introducing sulfonic acid groups into the N-terminus of a protein or a peptide. The method comprises a modification step to react a N-terminus in a protein or peptide with a compound A which includes disulfide group and a cleavage step to cleave a disulfide bond of the disulfide group to convert into a sulfonic acid group. The present invention also provides a method of analyzing proteins or peptides easily and effectively on mass spectrometry and an intermediate that can be used to effectively derivatize proteins or peptides as sulfonic acid derivatives.

摘要翻译： 本发明提供了将磺酸基团有效地引入蛋白质或肽的N-末端的方法。 该方法包括使蛋白质或肽中的N末端与包含二硫键的化合物A和切割二硫键的二硫键以切割成磺酸基团的切割步骤进行反应的修饰步骤。 本发明还提供了一种在质谱分析中容易且有效地分析蛋白质或肽的方法，以及可用于有效地将蛋白质或肽衍生为磺酸衍生物的中间体。

公开(公告)号：US07294707B2

公开(公告)日：2007-11-13

申请号：US10958298

申请日：2004-10-06

申请人： Takashi Nakazawa ,  Minoru Yamaguchi ,  Hiroki Kuyama ,  Eiji Ando ,  Norikazu Ueyama ,  Taka-aki Okamura ,  Shigemi Norioka

发明人： Takashi Nakazawa ,  Minoru Yamaguchi ,  Hiroki Kuyama ,  Eiji Ando ,  Norikazu Ueyama ,  Taka-aki Okamura ,  Shigemi Norioka

IPC分类号： C07K1/00

CPC分类号： C07K1/003

摘要： A simple and low-cost method of selectively modifying the C-terminal of a protein or peptide is provided. A method of modifying the C-terminal of a protein or peptide comprises forming an intramolecular oxazolone ring at the C-terminal of the protein or peptide that requires C-terminal modification, and then performing a ring-opening of the oxazolone ring to produce a protein or peptide with a modified C-terminal. Preferred forms include a method in which by reacting the oxazolone ring with a compound containing a nucleophilic group to effect an oxazolone ring-opening, a protein or peptide is produced in which the C-terminal is modified with the compound containing the nucleophilic group, as well as a method in which by reacting the oxazolone ring with an active esterifying agent to effect a ring-opening, the oxazolone is converted to an active ester, which by subsequent reaction with a compound containing a nucleophilic group, produces a protein or peptide in which the C-terminal has been modified with the compound containing the nucleophilic group.

摘要翻译： 提供了选择性修饰蛋白质或肽的C-末端的简单且低成本的方法。 修饰蛋白质或肽的C末端的方法包括在需要C末端修饰的蛋白质或肽的C-末端形成分子内的恶唑酮环，然后进行恶唑酮环的开环以产生 具有修饰C末端的蛋白质或肽。 优选的形式包括通过使恶唑酮环与含有亲核基团的化合物反应以进行恶唑酮开环的方法，制备其中C-末端用含有亲核基团的化合物修饰的蛋白质或肽作为 以及通过使恶唑酮环与活性酯化剂反应以开环的方法，将恶唑酮转化成活性酯，其随后与含有亲核基团的化合物反应，产生蛋白质或肽 其中C-末端已经与含有亲核基团的化合物一起被修饰。

公开(公告)号：US20050085622A1

公开(公告)日：2005-04-21

申请号：US10958298

申请日：2004-10-06

申请人： Takashi Nakazawa ,  Minoru Yamaguchi ,  Hiroki Kuyama ,  Eiji Ando ,  Norikazu Ueyama ,  Taka-aki Okamura ,  Shigemi Norioka

发明人： Takashi Nakazawa ,  Minoru Yamaguchi ,  Hiroki Kuyama ,  Eiji Ando ,  Norikazu Ueyama ,  Taka-aki Okamura ,  Shigemi Norioka

IPC分类号： C07K1/113 ,  C07K1/00 ,  C07K1/08 ,  C07K14/00

CPC分类号： C07K1/003

摘要： A simple and low-cost method of selectively modifying the C-terminal of a protein or peptide is provided. A method of modifying the C-terminal of a protein or peptide comprises forming an intramolecular oxazolone ring at the C-terminal of the protein or peptide that requires C-terminal modification, and then performing a ring-opening of the oxazolone ring to produce a protein or peptide with a modified C-terminal. Preferred forms include a method in which by reacting the oxazolone ring with a compound containing a nucleophilic group to effect an oxazolone ring-opening, a protein or peptide is produced in which the C-terminal is modified with the compound containing the nucleophilic group, as well as a method in which by reacting the oxazolone ring with an active esterifying agent to effect a ring-opening, the oxazolone is converted to an active ester, which by subsequent reaction with a compound containing a nucleophilic group, produces a protein or peptide in which the C-terminal has been modified with the compound containing the nucleophilic group.

摘要翻译： 提供了选择性修饰蛋白质或肽的C-末端的简单且低成本的方法。 修饰蛋白质或肽的C末端的方法包括在需要C末端修饰的蛋白质或肽的C-末端形成分子内的恶唑酮环，然后进行恶唑酮环的开环以产生 具有修饰C末端的蛋白质或肽。 优选的形式包括通过使恶唑酮环与含有亲核基团的化合物反应以进行恶唑酮开环的方法，制备其中C-末端用含有亲核基团的化合物修饰的蛋白质或肽作为 以及通过使恶唑酮环与活性酯化剂反应以开环的方法，将恶唑酮转化成活性酯，其随后与含有亲核基团的化合物反应，产生蛋白质或肽 其中C-末端已经与含有亲核基团的化合物一起被修饰。

公开(公告)号：US07041472B2

公开(公告)日：2006-05-09

申请号：US10739111

申请日：2003-12-19

申请人： Shigemi Norioka ,  Norikazu Ueyama ,  Taka-aki Okamura ,  Takashi Nakazawa ,  Minoru Yamaguchi ,  Eiji Ando

发明人： Shigemi Norioka ,  Norikazu Ueyama ,  Taka-aki Okamura ,  Takashi Nakazawa ,  Minoru Yamaguchi ,  Eiji Ando

IPC分类号： C12P21/06

CPC分类号： C12P21/06

摘要： The present invention provides a method for selectively collecting the N-terminal peptide fragments of a protein of interest whether or not the protein of interest is modified on the N-terminus. A method for selectively collecting the N-terminal peptide fragment of a protein, comprising: a protection step (1) of protecting side chain-amino groups of amino acid residues containing side chain-amino groups of a protein of interest to obtain a protected protein protected on the side chain-amino groups; a fragmentation step (2) of cleaving the protected protein into one N-terminal peptide fragment (a) containing the N-terminus of the peptide of interest and one or more of peptide fragments (b) other than the N-terminal peptide fragment (a); and a separation step (3) of separating the N-terminal peptide fragment (a) from the other peptide fragments (b) by selectively eluting the N-terminal peptide fragment (a) based on the difference in their reactivity or affinity to substrate, wherein the selective elution is achieved either by allowing the other peptide fragments (b) to bind to the substrate while allowing the N-terminal peptide fragment (a) to elute, or by allowing the N-terminal peptide fragment (a) to bind to the substrate while allowing the other peptide fragments (b) to elute and subsequently eluting the bound N-terminal peptide fragment (a).

摘要翻译： 本发明提供了一种用于选择性收集目的蛋白质的N-末端肽片段的方法，无论目的蛋白质是否在N末端被修饰。 一种用于选择性收集蛋白质的N-末端肽片段的方法，包括：保护步骤（1）保护含有目的蛋白质的侧链 - 氨基的氨基酸残基的侧链氨基以获得受保护的蛋白质 保护侧链氨基; 将保护的蛋白质切割成包含目标肽的N末端的一个N-末端肽片段（a）和除了N-末端肽片段之外的一个或多个肽片段（b）的片段化步骤（2） 一个）; 以及通过基于它们对底物的反应性或亲和力的差异来选择性地洗脱N末端肽片段（a），从而将N-末端肽片段（a）与其它肽片段（b）分离的分离步骤（3） 其中所述选择性洗脱通过使其它肽片段（b）与底物结合同时允许N-末端肽片段（a）洗脱，或通过使N-末端肽片段（a）与 同时允许其他肽片段（b）洗脱并随后洗脱结合的N-末端肽片段（a）。

公开(公告)号：US20050084927A1

公开(公告)日：2005-04-21

申请号：US10962575

申请日：2004-10-13

申请人： Shigemi Norioka ,  Minoru Yamaguchi ,  Hiroki Kuyama ,  Takashi Obama ,  Eiji Ando ,  Takashi Nakazawa ,  Norikazu Ueyama ,  Taka-aki Okamura

发明人： Shigemi Norioka ,  Minoru Yamaguchi ,  Hiroki Kuyama ,  Takashi Obama ,  Eiji Ando ,  Takashi Nakazawa ,  Norikazu Ueyama ,  Taka-aki Okamura

IPC分类号： C07K1/107 ,  C07K1/12 ,  C07K14/78 ,  C12N9/36 ,  C12P21/06 ,  C07K14/00

CPC分类号： C12N9/2462 ,  C07K1/1077 ,  C07K1/128 ,  C07K14/78

摘要： The present invention provides a method for effectively introducing sulfonic acid groups into the N-terminus of a protein or a peptide; a method capable of analyzing proteins or peptides easily and effectively on mass spectrometry; an intermediate that can be used to effectively derivatize proteins or peptides as sulfonic acid derivatives. A method for derivatizing a protein or peptide to a sulfonic acid derivative, comprising steps of: modification step to react a N-terminus in a protein or peptide with a compound A which includes disulfide group, to obtain a protein or peptide modified with the compound A at the N-terminus; and cleavage step to cleave a disulfide bond of the disulfide group to convert into a sulfonic acid group, thereby converting the modified protein or peptide into a sulfonic acid derivative. A method for analyzing the amino acid sequence of a protein or peptide, wherein the sulfonic acid derivative of a protein or a peptide obtained by the above method is subjected to mass spectrometry. A protein or peptide modified with a disulfide group-containing group at the N-terminus.

摘要翻译： 本发明提供了有效地将磺酸基引入蛋白质或肽的N末端的方法; 能够在质谱上容易且有效地分析蛋白质或肽的方法; 可用于有效地将蛋白质或肽衍生为磺酸衍生物的中间体。 一种将蛋白质或肽衍生为磺酸衍生物的方法，包括以下步骤：使蛋白质或肽中的N末端与包含二硫键的化合物A反应的修饰步骤，以获得用化合物修饰的蛋白质或肽 A在N端; 以及切割二硫键的二硫键转化为磺酸基的切割步骤，从而将修饰的蛋白质或肽转化为磺酸衍生物。 分析蛋白质或肽的氨基酸序列的方法，其中通过上述方法获得的蛋白质或肽的磺酸衍生物进行质谱分析。 在N末端用含二硫基的基团修饰的蛋白质或肽。

公开(公告)号：US20090325227A1

公开(公告)日：2009-12-31

申请号：US12090747

申请日：2006-10-23

申请人： Takashi Nakazawa ,  Mutsumi Oka ,  Kimiko Nishida ,  Minoru Yamaguchi ,  Hiroki Kuyama ,  Eiji Ando ,  Norikazu Ueyama ,  Takaaki Okamura ,  Susumu Tsunasawa

发明人： Takashi Nakazawa ,  Mutsumi Oka ,  Kimiko Nishida ,  Minoru Yamaguchi ,  Hiroki Kuyama ,  Eiji Ando ,  Norikazu Ueyama ,  Takaaki Okamura ,  Susumu Tsunasawa

IPC分类号： C12P21/00 ,  C07K1/107 ,  G01N33/68

CPC分类号： C07K17/00 ,  C07K1/1072 ,  C07K1/113

摘要： The present invention provides a method for inexpensively, easily and efficiently modifying the C-terminus of a protein or peptide; a method for easily and reliably isolating a C-terminal peptide fragment of a protein or peptide; and a method for rapidly, accurately and reliably determining an amino acid sequence of a protein or peptide by using a mass spectroscope. A method comprising the step of adding a formylation reagent and a catalyst to a protein or peptide to convert a carboxyl group into an aldehyde group. A method comprising the step of reacting a nucleophilic reagent with the aldehyde group to modify the C-terminus of the protein or peptide. A method comprising the step of reacting a support having a nucleophilic group to immobilize the protein or peptide. A method comprising the step of fragmenting the immobilized protein or peptide, washing the support, and isolating the C-terminal peptide fragment from the support. A method comprising the step of subjecting the isolated C-terminal peptide fragment to mass spectrometry and determining an amino acid sequence.

摘要翻译： 本发明提供了一种廉价，容易且有效地修饰蛋白质或肽的C末端的方法; 容易且可靠地分离蛋白质或肽的C末端肽片段的方法; 以及通过使用质谱仪快速，准确，可靠地测定蛋白质或肽的氨基酸序列的方法。 一种方法，其包括将甲酰化试剂和催化剂加入到蛋白质或肽中以将羧基转化为醛基的步骤。 一种包括使亲核试剂与醛基反应以修饰蛋白质或肽的C末端的步骤的方法。 一种包括使具有亲核基团的载体反应以固定蛋白质或肽的方法。 一种方法，其包括将固定的蛋白质或肽片段化，洗涤载体和从载体中分离C末端肽片段的步骤。 一种方法，包括使分离的C-末端肽片段进行质谱分析和测定氨基酸序列的步骤。

公开(公告)号：US20060241206A1

公开(公告)日：2006-10-26

申请号：US10552250

申请日：2004-04-08

申请人： Norikazu Ueyama ,  Hiroshi Mohri

发明人： Norikazu Ueyama ,  Hiroshi Mohri

IPC分类号： A61K6/00

CPC分类号： A61K6/0073 ,  A61K6/0023 ,  C08L33/00

摘要： A dental adhesive composition includes an organic polymer that contains a unit (A) containing a (substituted) carboxyl group, which is represented by formula (I), and a unit (B) containing a (substituted) carbamoyl group, which is represented by a formula (II). In the organic polymer, the sum of the two units (A) and (B) accounts for at least 20 mol % of all the units that constitute the organic polymer, and the ratio of unit (A)/unit (B) is within a range from 0.6/1.0 to 1.0/0.6. When the quantity of the unit having a smaller quantity than the other unit in the units (A) and (B) within the polymer is deemed 100 mol %, then in at least 70 mol % of the unit having a smaller quantity, the carbon bonded to the above (substituted) carboxyl group and the carbon bonded to the above (substituted) carbamoyl group are either directly adjacent, or bonded together via a methylene group or ethylene group.

摘要翻译： 牙科粘合剂组合物包括含有由式（I）表示的含有（取代的）羧基的单元（A）和含有（取代的）氨基甲酰基的单元（B）的有机聚合物，所述单元（B）由 式（II）。 在有机聚合物中，两个单元（A）和（B）的总和占构成有机聚合物的所有单元的至少20摩尔％，单元（A）/单元（B）的比例在 范围从0.6 / 1.0到1.0 / 0.6。 当聚合物内单元（A）和（B）中的其他单元的量少的单元的量被认为是100摩尔％时，则在至少70摩尔％的具有较小量的单元中，碳 与上述（取代的）羧基键合，并且与上述（取代的）氨基甲酰基键合的碳直接相邻或通过亚甲基或亚乙基键合在一起。

公开(公告)号：US20070293599A1

公开(公告)日：2007-12-20

申请号：US10555610

申请日：2004-04-14

申请人： Norikazu Ueyama ,  Hiroshi Mohri

发明人： Norikazu Ueyama ,  Hiroshi Mohri

IPC分类号： A61K6/087

CPC分类号： A61K6/0023 ,  A61K6/0276 ,  A61K6/06 ,  A61K6/083 ,  C08L33/00

摘要： A dental cement composition comprising an organic polymer and an inorganic powder including a polyvalent metal compound. The polymer comprises a unit (A) containing a (substituted) carboxyl group represented by a formula (I), and a unit (B) containing a (substituted) carbamoyl group represented by a formula (II). A sum of the units (A) and (B) accounts for at least 20 mol % of all units that form the organic polymer and a ratio of the unit (A)/unit (B) in the organic polymer is within a range from 0.6/1.0 to 1.0/0.6. When the quantity of the unit (A) or (B) having a smaller quantity than the other unit within the polymer is deemed 100 mol %, then in at least 70 mol % of the unit (A) or (B), carbons bonded to the (substituted) carboxyl group in the unit (A) and the (substituted) carbamoyl group in the unit (B) are either directly adjacent, or bonded together via a methylene group or ethylene group. (In formula (I), n represents either 0 or 1, X represents a hydrogen atom, —NH4, or 1/mM (wherein, M is a metal atom selected from the group consisting of alkali metals, alkali earth metals, transition metals, Zn and Cd, and m represents a valency of the metal), and R1 represents a hydrogen atom or a methyl group.) (In formula (II), n represents either 0 or 1, R2 represents a hydrogen atom or a methyl group, and R3 represents a hydrogen atom, an alkyl group, alkenyl group, aralkyl group or phosphonoxyalkyl group of 1 to 18 carbon atoms.)

摘要翻译： 一种牙科用水泥组合物，其包含有机聚合物和包含多价金属化合物的无机粉末。 聚合物包含含有式（I）所示的（取代）羧基的单元（A）和含有式（II）所示的（取代的）氨基甲酰基的单元（B）。 单位（A）和（B）的总和占构成有机聚合物的所有单元的至少20摩尔％，并且有机聚合物中单元（A）/单元（B）的比例在 0.6 / 1.0〜1.0 / 0.6。 当单体（A）或（B）的量小于聚合物内的其他单元的量为100mol％时，则在至少70mol％的单元（A）或（B）中，碳键合 单元（A）中的（取代的）羧基和单元（B）中的（取代的）氨基甲酰基直接相邻或通过亚甲基或亚乙基键合在一起。 （式（I）中，n表示0或1，X表示氢原子，-NH 4或1 / mM（式中，M表示选自碱金属 金属，碱土金属，过渡金属，Zn和Cd，m表示金属的化合价），R 1表示氢原子或甲基。（式（II）中， n表示0或1，R 2表示氢原子或甲基，R 3表示氢原子，烷基，烯基，芳烷基或 1至18个碳原子的膦酰氧基烷基）

公开(公告)号：US20080187839A1

公开(公告)日：2008-08-07

申请号：US11933507

申请日：2007-11-01

申请人： Shin NISHIMURA ,  Akira Satou ,  Takefumi Okumura ,  Makoto Morishima ,  Hitoshi Yamamoto ,  Norikazu Ueyama

发明人： Shin NISHIMURA ,  Akira Satou ,  Takefumi Okumura ,  Makoto Morishima ,  Hitoshi Yamamoto ,  Norikazu Ueyama

IPC分类号： H01M10/24

CPC分类号： C08F2/44 ,  H01B1/122

摘要： The disclosure discloses a polymer represented by the general formula, RpQZ . . . Mk+)n]m, wherein Rp is a residue of a polymer of a compound having a polymerizable unsaturated bond, Q is an organic residue of n+1 valences and connected directly or through another group to Rp by means of a single bond, Mk+ is a cation of k valence, Z is an organic function group capable of forming an ionic bond with cation Mk+ or an organic function group having a coordination capability with Mk+, and m, n and k are integers of one or more. The disclosure also discloses an intermediate of the polymer mentioned above.

摘要翻译： 本公开公开了一种由通式表示的聚合物，其中<？in-line-formula description =“In-Line Formulas”end =“lead”？> R p。 。 。 ＆lt;＆lt;＆gt;＆gt;＆lt;＆lt; k＆gt;＆lt;＆lt;＆lt; n + 其中R p是具有可聚合不饱和键的化合物的聚合物的残基，Q是n + 1价的有机残基，并且直接或通过另一个基团连接到R p SUB>通过单键，M k +是K价阳离子，Z是能够与阳离子M + k + +形成离子键的有机官能团，或 具有与M k + +的协调能力的有机功能组，m，n和k是一个或多个的整数。 本公开还公开了上述聚合物的中间体。

公开(公告)号：US07704642B2

公开(公告)日：2010-04-27

申请号：US11933507

申请日：2007-11-01

申请人： Shin Nishimura ,  Akira Satou ,  Takefumi Okumura ,  Makoto Morishima ,  Hitoshi Yamamoto ,  Norikazu Ueyama

发明人： Shin Nishimura ,  Akira Satou ,  Takefumi Okumura ,  Makoto Morishima ,  Hitoshi Yamamoto ,  Norikazu Ueyama

IPC分类号： H01M6/18

CPC分类号： C08F2/44 ,  H01B1/122

摘要： The disclosure discloses a polymer represented by the general formula, wherein Rp is a residue of a polymer of a compound having a polymerizable unsaturated bond, Q is an organic residue of n+1 valences and connected directly or through another group to Rp by means of a single bond, Mk+ is a cation of k valence, Z is an organic function group capable of forming an ionic bond with cation Mk+ or an organic function group having a coordination capability with Mk+, and m, n and k are integers of one or more. The disclosure also discloses an intermediate of the polymer mentioned above.

摘要翻译： 本发明公开了一种由通式表示的聚合物，其中Rp是具有可聚合不饱和键的化合物的聚合物的残基，Q是n + 1价的有机残基，并通过另一基团直接或通过另一个基团连接到Rp上，通过 单键，Mk +是k价的阳离子，Z是能够与阳离子Mk +形成离子键的有机官能团或与Mk +具有配位能力的有机官能团，m，n和k为1或 更多。 本公开还公开了上述聚合物的中间体。