公开(公告)号：US08097590B2

公开(公告)日：2012-01-17

申请号：US11596286

申请日：2005-05-10

申请人： Anne-Marie Pinel ,  Pascal Verdie ,  Pascaline Dubs ,  Jean Martinez ,  Gilles Subra

发明人： Anne-Marie Pinel ,  Pascal Verdie ,  Pascaline Dubs ,  Jean Martinez ,  Gilles Subra

IPC分类号： C07C229/00

CPC分类号： C07K5/0815 ,  A23L33/18 ,  A61K8/64 ,  A61K38/00 ,  A61K2800/57 ,  A61Q19/02 ,  C07K5/06078 ,  C07K5/06095

摘要： The invention relates to a dipeptide conjugate having general formula I, AA2-AA1-NH2, wherein A represent the radical corresponding to a monocarboxylic acid with general formula II, HOOC—R, in which: R represents a linear or branched aliphatic radical at C1-C24, which is optionally substituted by a hydroxyl group and which can comprise one or more unsaturations, preferably between 1 and 6 unsaturations, and/or which can comprise a phenyl group or lipoic acid or the reduced form thereof, dihydrolipoic acid or N-lipoyllysine; and AA1 and AA2 represent identical or different amino acids which are selected from the group containing Ala, Asn, Cys, Gln, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val, Asp, Glu, Arg, His, Lys, Orn, Dap, Dab, the corresponding homo-amino acids and the corresponding beta-amino acids in the form of enantiomers or diastereoisomers and mixtures thereof, including racemic mixtures.

摘要翻译： 本发明涉及具有通式I，AA2-AA1-NH2的二肽缀合物，其中A表示与通式II的单羧酸HOOC-R相应的基团，其中：R表示C1上的直链或支链脂族基团 -C 24，其任选被羟基取代并且可以包含一个或多个不饱和基团，优选1至6个不饱和基团，和/或其可以包含苯基或硫辛酸或其还原形式，二氢硫辛酸或N- 硫辛酰赖氨酸 AA1和AA2代表相同或不同的氨基酸，其选自含有Ala，Asn，Cys，Gln，Gly，Ile，Leu，Met，Phe，Pro，Ser，Thr，Trp，Tyr，Val，Asp，Glu ，Arg，His，Lys，Orn，Dap，Dab，相应的同型氨基酸和对映异构体或非对映异构体形式的相应β-氨基酸及其混合物，包括外消旋混合物。

公开(公告)号：US20070231284A1

公开(公告)日：2007-10-04

申请号：US11596286

申请日：2005-05-10

申请人： Anne-Marie Pinel ,  Pascal Verdie ,  Pascaline Dubs ,  Jean Martinez ,  Gilles Subra

发明人： Anne-Marie Pinel ,  Pascal Verdie ,  Pascaline Dubs ,  Jean Martinez ,  Gilles Subra

IPC分类号： C07C229/00 ,  A61K31/195 ,  A61K31/20 ,  C07C229/02 ,  A61K8/64 ,  A61Q19/02

CPC分类号： C07K5/0815 ,  A23L33/18 ,  A61K8/64 ,  A61K38/00 ,  A61K2800/57 ,  A61Q19/02 ,  C07K5/06078 ,  C07K5/06095

摘要： The invention relates to a dipeptide conjugate having general formula I, AA2-AA1-NH2, wherein A represent the radical corresponding to a monocarboxylic acid with general formula II, HOOC—R, in which: R represents a linear or branched aliphatic radical at C1-C24, which is optionally substituted by a hydroxyl group and which can comprise one or more unsaturations, preferably between 1 and 6 unsaturations, and/or which can comprise a phenyl group or lipoic acid or the reduced form thereof, dihydrolipoic acid or N-lipoyllysine; and AA1 and AA2 represent identical or different amino acids which are selected from the group containing Ala, Asn, Cys, Gln, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val, Asp, Glu, Arg, His, Lys, Orn, Dap, Dab, the corresponding homo-amino acids and the corresponding beta-amino acids in the form of enantiomers or diastereoisomers and mixtures thereof, including racemic mixtures.

摘要翻译： 本发明涉及具有通式I，AA2-AA1-NH 2的二肽缀合物，其中A代表相应于通式II的单羧酸HOOC-R的基团，其中：R表示 C 1 -C 12的直链或支链脂肪族基团，其任选被羟基取代，并且可以包含一个或多个不饱和度，优选1至6个不饱和度 ，和/或其可以包含苯基或硫辛酸或其还原形式，二氢硫辛酸或N-脂酰赖氨酸; AA1和AA2代表相同或不同的氨基酸，其选自含有Ala，Asn，Cys，Gln，Gly，Ile，Leu，Met，Phe，Pro，Ser，Thr，Trp，Tyr，Val，Asp，Glu ，Arg，His，Lys，Orn，Dap，Dab，相应的同型氨基酸和对映异构体或非对映异构体形式的相应β-氨基酸及其混合物，包括外消旋混合物。

公开(公告)号：US08017581B1

公开(公告)日：2011-09-13

申请号：US11596041

申请日：2005-05-10

申请人： Jean Martinez ,  Pascal Verdie ,  Pascaline Dubs ,  Anne-Marie Pinel ,  Gilles Subra

发明人： Jean Martinez ,  Pascal Verdie ,  Pascaline Dubs ,  Anne-Marie Pinel ,  Gilles Subra

IPC分类号： A61K38/00

CPC分类号： A61K47/542

摘要： The invention relates to a tripeptide conjugate having general formula I, A-AA1-AA2-AA3-NH2, wherein A represents the radical corresponding to a monocarboxylic acid with general formula II, HOOC—R, in which: R represents a linear or branched aliphatic radical at C1-C24, which is optionally substituted by a hydroxyl group and which can comprise one or more unsaturations, preferably between 1 and 6 unsaturations, lipoic acid or the reduced form thereof, dihydrolipoic acid, N-lipoyllysine, or phenylbutyric acid; and AA1, AA2 and AA3, which may be identical or different, represent independently of each other an amino acid selected from His, Phe, Ala, Arg, Lys, Orn, Trp, Nap, Tpi and Tic, on the condition that at least one of AA1, AA2 or AA3 represent Phe, preferably Dphe in the form of enantiomers or diastereoisomers and mixtures thereof, including racemic mixtures.

摘要翻译： 本发明涉及具有通式I，A-AA1-AA2-AA3-NH2的三肽缀合物，其中A表示与通式II的单羧酸HOOC-R相应的基团，其中：R表示直链或支链 C1-C24中的脂族基团，其任选被羟基取代，并且其可以包含一个或多个不饱和基团，优选1至6个不饱和基团，硫辛酸或其还原形式，二氢硫辛酸，N-硫代酰赖氨酸或苯基丁酸; 和AA1，AA2和AA3可以相同或不同，彼此独立地表示选自His，Phe，Ala，Arg，Lys，Orn，Trp，Nap，Tpi和Tic的氨基酸，条件是至少 AA1，AA2或AA3之一代表Phe，优选Dphe为对映体或非对映异构体及其混合物的形式，包括外消旋混合物。

公开(公告)号：US07785577B2

公开(公告)日：2010-08-31

申请号：US11596288

申请日：2005-05-10

申请人： Michel Hocquaux ,  Anne-Marie Pinel ,  Jean Martinez ,  Gilles Subra

发明人： Michel Hocquaux ,  Anne-Marie Pinel ,  Jean Martinez ,  Gilles Subra

IPC分类号： A61K8/64

CPC分类号： A61K47/54

摘要： The invention relates to a peptide of formula W-DPhe-Arg-Z (I) and to a conjugate thereof of a formula A-W-DPhe-Arg-Z (II), wherein A is a radical corresponding to a monocarboxylic acid of general formula HOOC—R (III), wherein R is an linear or branched possibly substituted by a hydroxy group aliphatic C1-C24 radical which can comprise one or several unsaturations, preferably from 1 to 6 unsaturations, a lipoic acid or the reduced form thereof, a dihydrolipoic acid, N-lipoyl-lysine or a phenylbutyric acid, W is His, Ala-His, Ala-Ala-His, Nle-Ala-His, DTrp-Ala-His, Nle-Trp-His, Lys, Ala-Lys, Nle-Ala-Lys, Orn, Ala-Orn, Nle-Ala-Orn, Ala, Nle-Ala-Ala, Arg, Ala-Arg. Nle-Ala-Arg, Nle-Ala-DTrp or a bond in case of compounds of formula (II), Z is NH2, OH and OR, wherein R is a linear or branched aliphatic C1-C24 radical, TrpNH2, NapNH2, TpiNH2, TicNH2, AlaNH2i TrpOH, NapOH, TpiOH, TicOH, AlaOH, PheNH2, or PheOH, exempting a peptidic conjugate for which A is a radical corresponding to an acetic acid, W is Nle-Ala-His and Z is TrpNH2 in the form of enantiomers or diastereoisomer and the mixtures thereof including racemic mixtures. The use of the inventive compounds for cosmetically fighting against canities is also disclosed.

摘要翻译： 本发明涉及式W-DPhe-Arg-Z（I）的肽及其与式AW-DPhe-Arg-Z（II）的结合物，其中A是相应于通式 HOOC-R（III），其中R是可以被羟基脂族C 1 -C 24基取代的直链或支链，其可以包含一个或多个不饱和基团，优选1至6个不饱和基团，硫辛酸或其还原形式， 二氢硫辛酸，N-脂酰赖氨酸或苯丁酸，W是His，Ala-His，Ala-Ala-His，Nle-Ala-His，DTrp-Ala-His，Nle-Trp-His，Lys，Ala-Lys ，Nle-Ala-Lys，Orn，Ala-Orn，Nle-Ala-Orn，Ala，Nle-Ala-Ala，Arg，Ala-Arg。 Nle-Ala-Arg，Nle-Ala-DTrp或在式（II）化合物的情况下为键，Z为NH 2，OH和OR，其中R为直链或支链脂族C 1 -C 24基团，TrpNH 2，NapNH 2，TpiNH 2 ，TicNH2，AlaNH2i TrpOH，NapOH，TpiOH，TicOH，AlaOH，PheNH2或PheOH，免除其中A是对应于乙酸的基团的肽结合物，W是Nle-Ala-His，Z是TrpNH2，其形式为 对映异构体或非对映异构体及其混合物，包括外消旋混合物。 还公开了本发明化合物用于美容化妆品的用途。

公开(公告)号：US20080200396A1

公开(公告)日：2008-08-21

申请号：US11596288

申请日：2005-05-10

申请人： Michel Hocquaux ,  Anne-Marie Pinel ,  Jean Martinez ,  Gilles Subra

发明人： Michel Hocquaux ,  Anne-Marie Pinel ,  Jean Martinez ,  Gilles Subra

IPC分类号： A61K8/64 ,  A61Q5/00

CPC分类号： A61K47/54

摘要： The invention relates to a peptide of formula W-DPhe-Arg-Z (I) and to a conjugate thereof of a formula A-W-DPhe-Arg-Z (II), wherein A is a radical corresponding to a nionocarboxylic acid of general formula HOOC—R (III), wherein R is an linear or branched possibly substituted by a hydroxy group aliphatic C1-C24 radical which can comprise one or several unsaturations, preferably from 1 to 6 unsaturations, a lipoic acid or the reduced form thereof, a dihydrolipoic acid, N-lipoyl-lysine or a phenylbutyric acid, W is His, Ala-His, Ala-Ala-His, Nle-Ala-His, DTrp-Ala-His, Nle-Trp-His, Lys, Ala-Lys, Nle-Ala-Lys, Orn, Ala-Orn, Nle-Ala-Orn, Ala, Nle-Ala-Ala, Arg, Ala-Arg. Nle-Ala-Arg, Nle-Ala-DTrp or a bond in case of compounds of formula (II), Z is NH2, OH and OR, wherein R is a linear or branched aliphatic C1-C24 radical, TrpNH2, NapNH2, TpiNH2, TicNH2, AlaNH2i TrpOH, NapOH, TpiOH, TicOH, AlaOH, PheNH2, or PheOH, exempting a peptidic conjugate for which A is a radical corresponding to an acetic acid, W is Nle-Ala-His and Z is TrpNH2 in the form of enantiomers or diastereoisomer and the mixtures thereof including racemic mixtures. The use of the inventive compounds for cosmetically fighting against canities is also disclosed.

摘要翻译： 本发明涉及式W-DPhe-Arg-Z（I）的肽及其与式AW-DPhe-Arg-Z（II）的共轭物，其中A是相应于通式 HOOC-R（III），其中R是可以被羟基脂族C 1 -C 24 - 基团取代的直链或支链，其可以包含一个或几个不饱和基团，优选 1至6个不饱和键，硫辛酸或其还原形式，二氢硫辛酸，N-脂酰赖氨酸或苯丁酸，W是His，Ala-His，Ala-Ala-His，Nle-Ala-His，DTrp -Ale-His，Nle-Trp-His，Lys，Ala-Lys，Nle-Ala-Lys，Orn，Ala-Orn，Nle-Ala-Orn，Ala，Nle-Ala-Ala，Arg，Ala-Arg。 Nle-Ala-Arg，Nle-Ala-DTrp或在式（II）化合物的情况下为键，Z为NH 2，OH和OR，其中R为直链或支链脂族C 1， N，N，N，N，N，N，N，N，N， 2 N，AlaNH 2，TrpOH，NapOH，TpiOH，TicOH，AlaOH，PheNH 2 H或PheOH，可以免除A为 对应于乙酸的基团，W是Nle-Ala-His，Z是对映异构体或非对映异构体形式的TrpNH 2 H 2，其混合物包括外消旋混合物。 还公开了本发明化合物用于美容化妆品的用途。

公开(公告)号：US08546533B2

公开(公告)日：2013-10-01

申请号：US13061080

申请日：2009-08-28

申请人： Jean Martinez ,  Pawel Zajdel ,  Maciej Pawlowski ,  Gilles Subra

发明人： Jean Martinez ,  Pawel Zajdel ,  Maciej Pawlowski ,  Gilles Subra

IPC分类号： C07K1/02

CPC分类号： C07D211/60 ,  C07K2/00

摘要： The present invention relates to a pipecolic linker and its use as a solid-phase linker in organic synthesis. Said pipecolic solid-phase linker may be used for coupling functional groups chosen between primary amines, secondary amines, aromatic amines, alcohols, phenols and thiols. In particular, said pipecolic solid-phase linker may be used for peptide or pseudopeptide synthesis, such as the reverse N to C peptide synthesis or the retro-inverso peptide synthesis, or for the synthesis of small organic molecules.

摘要翻译： 本发明涉及一种管式接头及其在有机合成中作为固相接头的用途。 所述管式固相接头可用于偶联在伯胺，仲胺，芳族胺，醇，酚和硫醇之间选择的官能团。 特别地，所述皮肤固相接头可用于肽或假肽合成，例如反向N至C肽合成或逆转肽合成，或用于合成小有机分子。

公开(公告)号：US20110003943A1

公开(公告)日：2011-01-06

申请号：US12308449

申请日：2007-06-14

申请人： Jean Martinez ,  Gilles Subra ,  Michèle Cristau ,  Sonia Cantel

发明人： Jean Martinez ,  Gilles Subra ,  Michèle Cristau ,  Sonia Cantel

IPC分类号： C08F283/04 ,  A61K38/08

CPC分类号： C07K1/1133 ,  Y02P20/55 ,  Y02P20/582

摘要： The present invention relates to a supported oxidation reactant of formula (I): R-[Met(O)k]n-X-(I) in which: —R represents a hydrogen atom or an amine function-protecting group, —[Met(O)] represents an oxidized methionine residue of formula—k is 1 or 2—represents a solid or soluble support used in organic synthesis, —X represents a radical derived from a function of the type amine or hydroxyl, or halogeno, capable of anchoring methionine, it being understood that this function capable of anchoring methionine can be separated from the support by means of a functionalized arm or a spacer, and—n is an integer greater than or equal to 1. The invention also relates to the use of a supported oxidation reactant of formula (I), for the formation of intramolecular disulfide bridges, in particular in peptides and/or proteins.

摘要翻译： 本发明涉及式（I）的支持氧化反应物：R- [Met（O）k] nX-（I）其中：-R表示氢原子或胺官能保护基， - [Met O）]表示式-k的氧化甲硫氨酸残基为1或2-代表有机合成中使用的固体或可溶性载体，-X表示衍生自胺或羟基或卤代的功能的基团，或能够锚定 甲硫氨酸，可以理解，能够锚定甲硫氨酸的该功能可以通过官能化的臂或间隔物与支持物分离，并且-n是大于或等于1的整数。本发明还涉及使用 支持式（I）的氧化反应物，用于形成分子内二硫键，特别是肽和/或蛋白质。

公开(公告)号：US20110152464A1

公开(公告)日：2011-06-23

申请号：US13061080

申请日：2009-08-28

申请人： Jean Martinez ,  Pawel Zajdel ,  Maciej Pawlowski ,  Gilles Subra

发明人： Jean Martinez ,  Pawel Zajdel ,  Maciej Pawlowski ,  Gilles Subra

IPC分类号： C08F12/28 ,  C07D211/60 ,  C07K1/10

CPC分类号： C07D211/60 ,  C07K2/00

摘要： The present invention relates to a pipecolic linker and its use as a solid-phase linker in organic synthesis. Said pipecolic solid-phase linker may be used for coupling functional groups chosen between primary amines, secondary amines, aromatic amines, alcohols, phenols and thiols. In particular, said pipecolic solid-phase linker may be used for peptide or pseudopeptide synthesis, such as the reverse N to C peptide synthesis or the retro-inverso peptide synthesis, or for the synthesis of small organic molecules.

摘要翻译： 本发明涉及一种管式接头及其在有机合成中作为固相接头的用途。 所述管式固相接头可用于偶联在伯胺，仲胺，芳族胺，醇，酚和硫醇之间选择的官能团。 特别地，所述皮肤固相接头可用于肽或假肽合成，例如反向N至C肽合成或逆转肽合成，或用于合成小有机分子。

公开(公告)号：US20120070856A1

公开(公告)日：2012-03-22

申请号：US13254500

申请日：2010-03-04

申请人： Jean Martinez ,  Gilles Subra ,  Christine Goubet ,  David Paramelle ,  Eric Forest ,  Michaël Heymann ,  Christophe Geourjon

发明人： Jean Martinez ,  Gilles Subra ,  Christine Goubet ,  David Paramelle ,  Eric Forest ,  Michaël Heymann ,  Christophe Geourjon

IPC分类号： C12Q1/37 ,  C07D207/46 ,  C07D403/12

CPC分类号： C07D207/46

摘要： The invention relates to a protein cross-linking agent of the formula, where R1 is an aryl group optionally substituted once or several times by a grouping selected from the group consisting of hydroxy, C1-C4 alkyl, OBoc, SO3Na, Deu, and C1-C4 alkoxy groupings, R2 is N, (III), or (IV), n and in are identical or different integers between 0 and 10, p is an integer between 0 and 5, k is 0, 1, 2 or 3, and X and X′ are identical or different and are a reactive function of the proteins. The invention also relates to a method for the structural analysis of a protein or a protein complex.

摘要翻译： 本发明涉及下式的蛋白质交联剂，其中R 1是任选地被选自羟基，C 1 -C 4烷基，OBoc，SO 3 N a，Deu和C 1的基团取代一次或几次的芳基 -C4烷氧基，R2是N，（III）或（IV），n和in是0和10之间的相同或不同的整数，p是0和5之间的整数，k是0,1,2或3， X和X'相同或不同，并且是蛋白质的反应性功能。 本发明还涉及蛋白质或蛋白质复合物的结构分析方法。