公开(公告)号：US08440169B2

公开(公告)日：2013-05-14

申请号：US12559089

申请日：2009-09-14

申请人： Masatsune Kainosho ,  Tsutomu Terauchi

发明人： Masatsune Kainosho ,  Tsutomu Terauchi

IPC分类号： A61B5/055 ,  C12P13/04 ,  C12P9/00 ,  C07K1/00

CPC分类号： C07C47/575 ,  C07B2200/05 ,  C07C47/54 ,  C07C229/08 ,  C07C229/36 ,  C07D209/20 ,  C07D233/64 ,  C07K1/00 ,  C12P21/02 ,  G01N24/08 ,  G01R33/465

摘要： The present invention herein provides, for instance, a stable isotope-labeled phenylalanine wherein a carbon atom of the phenyl group linked to an amino acid residue is 13C, 2 to 4 carbon atoms of the remaining 5 carbon atoms constituting the phenyl group are 12C atoms to which deuterium atoms are bonded, and the remaining carbon atoms are 13C atoms to which hydrogen atoms are linked, and a stable isotope-labeled tyrosine wherein a carbon atom of the phenyl group linked to an amino acid residue is 13C, the carbon atom bonded to the hydroxyl group (OH group) of the phenyl group is 12C or 13C, 2 to 4 carbon atoms of the remaining 4 carbon atoms constituting the phenyl group are 12C atoms to which deuterium atoms are bonded, and the remaining carbon atoms are 13C atoms to which hydrogen atoms are linked. The stable isotope-labeled amino acid permits the elimination of such a conventional problem concerning the complexity of the NMR signals ascribed to aromatic rings, the complexity being a principal cause of making the NMR analysis difficult, encountered when using the conventional uniformly labeled amino acid residue. Moreover, the isotope-labeled amino acid likewise permits the substantial improvement of the sensitivity thereof to the NMR spectroscopic analysis.

公开(公告)号：US08022173B2

公开(公告)日：2011-09-20

申请号：US12198462

申请日：2008-08-26

申请人： Masatsune Kainosho ,  Tsutomu Terauchi

发明人： Masatsune Kainosho ,  Tsutomu Terauchi

IPC分类号： C07K14/00 ,  C07C229/00

CPC分类号： C07K1/13 ,  C07B59/00 ,  C07B59/001 ,  C07B2200/05 ,  C07C229/08 ,  C07C229/22 ,  C07C229/24 ,  C07C229/26 ,  C07C237/06 ,  C07C279/14 ,  C07C323/58 ,  C07D207/16 ,  C07D209/20 ,  C07D233/64 ,  G01N24/08 ,  G01N24/087 ,  G01R33/465

摘要： The present invention herein provides a combination of stable isotope-labeled aliphatic amino acids, which permits the structural analysis of a high molecular weight protein, in particular, a high molecular weight protein whose molecular weight exceeds 60 kDa. This is a combination of stable isotope-labeled amino acids which is characterized in that arginine (Arg), glutamine (Gln), glutamic acid (Glu), lysine (Lys), methionine (Met) and proline (Pro) satisfy the following requirements concerning the labelling pattern: (b) one of the methylene hydrogen atoms of at least one of the methylene groups is deuterated and the both of the two methylene hydrogen atoms of at least one of the methylene groups are likewise deuterated; and (d) when they each have a methyl group, the hydrogen atoms of the methyl group except for one of the same are deuterated, or the methyl group is completely deuterated.

摘要翻译： 本发明提供稳定同位素标记的脂族氨基酸的组合，其允许高分子量蛋白质，特别是其分子量超过60kDa的高分子量蛋白质的结构分析。 这是稳定同位素标记的氨基酸的组合，其特征在于精氨酸（Arg），谷氨酰胺（Gln），谷氨酸（Glu），赖氨酸（Lys），甲硫氨酸（Met）和脯氨酸（Pro）满足以下要求 关于标记图案：（b）至少一个亚甲基的亚甲基氢原子之一是氘化的，并且至少一个亚甲基的两个亚甲基氢原子同样是氘化的; 和（d）当它们各自具有甲基时，甲基的除了其中之一的氢原子是氘化的，或甲基完全氘化。

公开(公告)号：US07608248B2

公开(公告)日：2009-10-27

申请号：US11414756

申请日：2006-04-28

申请人： Masatsune Kainosho ,  Tsutomu Terauchi

发明人： Masatsune Kainosho ,  Tsutomu Terauchi

IPC分类号： A61B5/055 ,  C12P13/04 ,  C12P9/00 ,  C07K1/00

CPC分类号： C07C47/575 ,  C07B2200/05 ,  C07C47/54 ,  C07C229/08 ,  C07C229/36 ,  C07D209/20 ,  C07D233/64 ,  C07K1/00 ,  C12P21/02 ,  G01N24/08 ,  G01R33/465

摘要： The present invention herein provides, for instance, a stable isotope-labeled phenylalanine wherein a carbon atom of the phenyl group linked to an amino acid residue is 13C, 2 to 4 carbon atoms of the remaining 5 carbon atoms constituting the phenyl group are 12C atoms to which deuterium atoms are bonded, and the remaining carbon atoms are 13C atoms to which hydrogen atoms are linked, and a stable isotope-labeled tyrosine wherein a carbon atom of the phenyl group linked to an amino acid residue is 13C, the carbon atom bonded to the hydroxyl group (OH group) of the phenyl group is 12C or 13C, 2 to 4 carbon atoms of the remaining 4 carbon atoms constituting the phenyl group are 12C atoms to which deuterium atoms are bonded, and the remaining carbon atoms are 13C atoms to which hydrogen atoms are linked. The stable isotope-labeled amino acid permits the elimination of such a conventional problem concerning the complexity of the NMR signals ascribed to aromatic rings, the complexity being a principal cause of making the NMR analysis difficult, encountered when using the conventional uniformly labeled amino acid residue. Moreover, the isotope-labeled amino acid likewise permits the substantial improvement of the sensitivity thereof to the NMR spectroscopic analysis.

摘要翻译： 本发明提供例如稳定同位素标记的苯丙氨酸，其中与氨基酸残基连接的苯基的碳原子为13 C，构成苯基的剩余5个碳原子的2至4个碳原子为12 C原子 氘原子键合在其上，剩余的碳原子是与氢原子连接的13 C原子，和与氨基酸残基连接的苯基的碳原子为13 C的稳定的同位素标记的酪氨酸，碳原子键合 苯基的羟基（OH基）为12℃或13℃，构成苯基的剩余4个碳原子的2〜4个碳原子为氘原子键合的12 C原子，剩余碳原子为13 C原子 氢原子连接在其上。 稳定的同位素标记的氨基酸允许消除关于归因于芳环的NMR信号的复杂性的常规问题，当使用常规的均匀标记的氨基酸残基时，复杂性是使NMR分析困难的主要原因 。 此外，同位素标记的氨基酸同样允许其对NMR光谱分析的敏感性的显着提高。

公开(公告)号：US20060194328A1

公开(公告)日：2006-08-31

申请号：US11414756

申请日：2006-04-28

申请人： Masatsune Kainosho ,  Tsutomu Terauchi

发明人： Masatsune Kainosho ,  Tsutomu Terauchi

IPC分类号： C07K1/02 ,  G01N33/00 ,  C07D233/61 ,  C07D209/20

CPC分类号： C07C47/575 ,  C07B2200/05 ,  C07C47/54 ,  C07C229/08 ,  C07C229/36 ,  C07D209/20 ,  C07D233/64 ,  C07K1/00 ,  C12P21/02 ,  G01N24/08 ,  G01R33/465

摘要： The present invention herein provides, for instance, a stable isotope-labeled phenylalanine wherein a carbon atom of the phenyl group linked to an amino acid residue is 13C, 2 to 4 carbon atoms of the remaining 5 carbon atoms constituting the phenyl group are 12C atoms to which deuterium atoms are bonded, and the remaining carbon atoms are 13C atoms to which hydrogen atoms are linked, and a stable isotope-labeled tyrosine wherein a carbon atom of the phenyl group linked to an amino acid residue is 13C, the carbon atom bonded to the hydroxyl group (OH group) of the phenyl group is 12C or 13C, 2 to 4 carbon atoms of the remaining 4 carbon atoms constituting the phenyl group are 12C atoms to which deuterium atoms are bonded, and the remaining carbon atoms are 13C atoms to which hydrogen atoms are linked. The stable isotope-labeled amino acid permits the elimination of such a conventional problem concerning the complexity of the NMR signals ascribed to aromatic rings, the complexity being a principal cause of making the NMR analysis difficult, encountered when using the conventional uniformly labeled amino acid residue. Moreover, the isotope-labeled amino acid likewise permits the substantial improvement of the sensitivity thereof to the NMR spectroscopic analysis.

摘要翻译： 本发明提供了例如稳定同位素标记的苯丙氨酸，其中与氨基酸残基连接的苯基的碳原子是剩余的5碳的2至4个碳原子 构成苯基的原子是氘原子键合的12个C原子，剩余的碳原子是与氢原子连接的13个C原子，和一个稳定的同位素 标记的酪氨酸，其中与氨基酸残基连接的苯基的碳原子为13 C，与苯基的羟基（OH基）键合的碳原子为12， 构成苯基的剩余的4个碳原子的2至4个碳原子是与氘原子键合的12个C原子，并且 剩余的碳原子是与氢原子连接的13个C原子。 稳定的同位素标记的氨基酸允许消除关于归因于芳环的NMR信号的复杂性的常规问题，当使用常规的均匀标记的氨基酸残基时，复杂性是使NMR分析困难的主要原因 。 此外，同位素标记的氨基酸同样允许其对NMR光谱分析的敏感性的显着提高。

公开(公告)号：US20100056799A1

公开(公告)日：2010-03-04

申请号：US12559089

申请日：2009-09-14

申请人： Masatsune Kainosho ,  Tsutomu Terauchi

发明人： Masatsune Kainosho ,  Tsutomu Terauchi

IPC分类号： C07D233/56 ,  C07C229/36 ,  C07D209/20

CPC分类号： C07C47/575 ,  C07B2200/05 ,  C07C47/54 ,  C07C229/08 ,  C07C229/36 ,  C07D209/20 ,  C07D233/64 ,  C07K1/00 ,  C12P21/02 ,  G01N24/08 ,  G01R33/465

摘要： The present invention herein provides, for instance, a stable isotope-labeled phenylalanine wherein a carbon atom of the phenyl group linked to an amino acid residue is 13C, 2 to 4 carbon atoms of the remaining 5 carbon atoms constituting the phenyl group are 12C atoms to which deuterium atoms are bonded, and the remaining carbon atoms are 13C atoms to which hydrogen atoms are linked, and a stable isotope-labeled tyrosine wherein a carbon atom of the phenyl group linked to an amino acid residue is 13C, the carbon atom bonded to the hydroxyl group (OH group) of the phenyl group is 12C or 13C, 2 to 4 carbon atoms of the remaining 4 carbon atoms constituting the phenyl group are 12C atoms to which deuterium atoms are bonded, and the remaining carbon atoms are 13C atoms to which hydrogen atoms are linked. The stable isotope-labeled amino acid permits the elimination of such a conventional problem concerning the complexity of the NMR signals ascribed to aromatic rings, the complexity being a principal cause of making the NMR analysis difficult, encountered when using the conventional uniformly labeled amino acid residue. Moreover, the isotope-labeled amino acid likewise permits the substantial improvement of the sensitivity thereof to the NMR spectroscopic analysis.

摘要翻译： 本发明提供例如稳定同位素标记的苯丙氨酸，其中与氨基酸残基连接的苯基的碳原子为13 C，构成苯基的剩余5个碳原子的2至4个碳原子为12 C原子 氘原子键合在其上，剩余的碳原子是与氢原子连接的13 C原子，和与氨基酸残基连接的苯基的碳原子为13 C的稳定的同位素标记的酪氨酸，碳原子键合 苯基的羟基（OH基）为12℃或13℃，构成苯基的剩余4个碳原子的2〜4个碳原子为氘原子键合的12 C原子，剩余碳原子为13 C原子 氢原子连接在其上。 稳定的同位素标记的氨基酸允许消除关于归因于芳环的NMR信号的复杂性的常规问题，当使用常规的均匀标记的氨基酸残基时，复杂性是使NMR分析困难的主要原因 。 此外，同位素标记的氨基酸同样允许其对NMR光谱分析的敏感性的显着提高。

公开(公告)号：US20050084452A1

公开(公告)日：2005-04-21

申请号：US10872163

申请日：2004-06-18

申请人： Masatsune Kainosho ,  Tsutomu Terauchi

发明人： Masatsune Kainosho ,  Tsutomu Terauchi

IPC分类号： C07B59/00 ,  C07C51/09 ,  C07C229/08 ,  C07C229/22 ,  C07C229/24 ,  C07C229/26 ,  C07C229/36 ,  C07C323/58 ,  G01N24/08 ,  A61K49/00 ,  C07K14/00

CPC分类号： C07B59/001 ,  C07B2200/05 ,  C07C51/09 ,  C07C229/08 ,  C07C229/22 ,  C07C229/24 ,  C07C229/26 ,  C07C229/36 ,  C07C323/58 ,  C07K1/13 ,  G01N24/08 ,  C07C57/15

摘要： The present invention provides a stable isotope-labeled amino acid which is at least one of amino acids constituting a protein and which has at least one of the following labeling patterns: (a) hydrogen atoms except at least one hydrogen atom in one or more methylene groups are deuterated, (b) hydrogen atoms in one of prochiral gem-methyl groups are completely deuterated, (c) hydrogen atoms in prochiral methyl groups are partially deuterated, and (d) all hydrogen atoms except one of them in methyl group are deuterated and hydrogen atoms in the aromatic ring are partially deuterated. With the stable isotope-labeled amino acid, the deuteration of protein can be attained without damaging the NMR sensitivity of remaining hydrogen nucleus and, in addition, the rapid, accurate analysis of NMR spectrum of a high-molecular protein which is beyond the limitation in the prior art and the determination of the stereo-structure can be performed at the same time.

摘要翻译： 本发明提供了一种稳定同位素标记的氨基酸，其是构成蛋白质的氨基酸中的至少一种，并且具有以下标记模式中的至少一种：（a）氢原子，除了一个或多个亚甲基中的至少一个氢原子 de uter uter de de de de de ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated 并且芳环中的氢原子被部分氘化。 利用稳定的同位素标记的氨基酸，可以获得蛋白质的氘化，而不会损害剩余氢核的核磁共振灵敏度，此外，快速准确地分析高分子蛋白质的NMR光谱，超过了 现有技术和立体结构的确定可以同时进行。

公开(公告)号：US20090075388A1

公开(公告)日：2009-03-19

申请号：US12198462

申请日：2008-08-26

申请人： Masatsune Kainosho ,  Tsutomu Terauchi

发明人： Masatsune Kainosho ,  Tsutomu Terauchi

IPC分类号： G01N33/68 ,  C12N15/87 ,  C12P21/00

CPC分类号： C07K1/13 ,  C07B59/00 ,  C07B59/001 ,  C07B2200/05 ,  C07C229/08 ,  C07C229/22 ,  C07C229/24 ,  C07C229/26 ,  C07C237/06 ,  C07C279/14 ,  C07C323/58 ,  C07D207/16 ,  C07D209/20 ,  C07D233/64 ,  G01N24/08 ,  G01N24/087 ,  G01R33/465

摘要： The present invention herein provides a combination of stable isotope-labeled aliphatic amino acids, which permits the structural analysis of a high molecular weight protein, in particular, a high molecular weight protein whose molecular weight exceeds 60 kDa. This is a combination of stable isotope-labeled amino acids which is characterized in that arginine (Arg), glutamine (Gln), glutamic acid (Glu), lysine (Lys), methionine (Met) and proline (Pro) satisfy the following requirements concerning the labelling pattern:(b) one of the methylene hydrogen atoms of at least one of the methylene groups is deuterated and the both of the two methylene hydrogen atoms of at least one of the methylene groups are likewise deuterated; and (d) when they each have a methyl group, the hydrogen atoms of the methyl group except for one of the same are deuterated, or the methyl group is completely deuterated.

摘要翻译： 本发明提供稳定同位素标记的脂族氨基酸的组合，其允许高分子量蛋白质，特别是其分子量超过60kDa的高分子量蛋白质的结构分析。 这是稳定同位素标记的氨基酸的组合，其特征在于精氨酸（Arg），谷氨酰胺（Gln），谷氨酸（Glu），赖氨酸（Lys），甲硫氨酸（Met）和脯氨酸（Pro）满足以下要求 关于标记图案：（b）至少一个亚甲基的亚甲基氢原子之一是氘化的，并且至少一个亚甲基的两个亚甲基氢原子同样是氘化的; 和（d）当它们各自具有甲基时，甲基的除了其中之一的氢原子是氘化的，或甲基完全氘化。

公开(公告)号：US07022310B2

公开(公告)日：2006-04-04

申请号：US10872163

申请日：2004-06-18

申请人： Masatsune Kainosho ,  Tsutomu Terauchi

发明人： Masatsune Kainosho ,  Tsutomu Terauchi

IPC分类号： A61B5/055 ,  C12P13/04 ,  C12P9/00 ,  C07K1/00

CPC分类号： C07B59/001 ,  C07B2200/05 ,  C07C51/09 ,  C07C229/08 ,  C07C229/22 ,  C07C229/24 ,  C07C229/26 ,  C07C229/36 ,  C07C323/58 ,  C07K1/13 ,  G01N24/08 ,  C07C57/15

摘要： The present invention provides a stable isotope-labeled amino acid which is at least one of amino acids constituting a protein and which has at least one of the following labeling patterns: (a) hydrogen atoms except at least one hydrogen atom in one or more methylene groups are deuterated, (b) hydrogen atoms in one of prochiral gem-methyl groups are completely deuterated, (c) hydrogen atoms in prochiral methyl groups are partially deuterated, and (d) all hydrogen atoms except one of them in methyl group are deuterated and hydrogen atoms in the aromatic ring are partially deuterated. With the stable isotope-labeled amino acid, the deuteration of protein can be attained without damaging the NMR sensitivity of remaining hydrogen nucleus and, in addition, the rapid, accurate analysis of NMR spectrum of a high-molecular protein which is beyond the limitation in the prior art and the determination of the stereo-structure can be performed at the same time.

摘要翻译： 本发明提供了一种稳定同位素标记的氨基酸，其是构成蛋白质的氨基酸中的至少一种，并且具有以下标记模式中的至少一种：（a）氢原子，除了一个或多个亚甲基中的至少一个氢原子 de uter uter de de de de de ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated ated 并且芳环中的氢原子被部分氘化。 利用稳定的同位素标记的氨基酸，可以获得蛋白质的氘化，而不会损害剩余氢核的核磁共振灵敏度，此外，快速准确地分析高分子蛋白质的NMR光谱，超过了 现有技术和立体结构的确定可以同时进行。

公开(公告)号：US4294754A

公开(公告)日：1981-10-13

申请号：US27029

申请日：1979-04-04

申请人： Yoshiyuki Takahara ,  Yoshiteru Hirose ,  Yoko Takeuchi ,  Asao Murai ,  Masatsune Kainosho ,  Sawao Murao

发明人： Yoshiyuki Takahara ,  Yoshiteru Hirose ,  Yoko Takeuchi ,  Asao Murai ,  Masatsune Kainosho ,  Sawao Murao

IPC分类号： A61K35/74 ,  A61K38/00 ,  A61P31/04 ,  C07K7/06 ,  C07K11/00 ,  C07K11/02 ,  C07K14/195 ,  C07K14/41 ,  C12P21/04 ,  C07C103/52

CPC分类号： C07K7/06 ,  C12R1/09 ,  Y10S930/19 ,  Y10S930/27

摘要： A purified ring peptide antibiotic of the following empirical formula:N.alpha.-(3-hydroxy-4-methyl-1-oxohexyl)-L-.alpha.,.gamma.-diaminobutyryl-L-isoleucyl-L-.alpha.,.gamma.-diaminobutyryl-D-phenylalanyl-L-leucyl-L-.alpha.,.gamma.-diaminobutyryl-D-valyl-L-leucyl-L-serine (9-1)-lactoneand which has the following structural formula: ##STR1## and wherein Dab represents 2,4-diamino butyric acid.

摘要翻译： 具有以下经验式的纯化的环肽抗生素：Nα-（3-羟基-4-甲基-1-氧代己基）-L-α，γ-二氨基丁酰基-L-异亮氨酰-L-α，γ-二氨基丁酰基-D- 苯丙氨酰-L-亮氨酰-L-α，γ-二氨基丁酰-D-缬氨酰-L-亮氨酰-L-丝氨酸（9-1） - 内酯，其具有以下结构式：其中Dab表示2,4 - 二氨基丁酸。