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1. 发明申请

WO2003099862A1 EXPORT AND MODIFICATION OF (POLY)PEPTIDES IN THE LANTIBIOTIC WAY 审中-公开
标题翻译：（POLY）PEPTIDES在生态方式的出口和修改
公开(公告)号：WO2003099862A1
公开(公告)日：2003-12-04
申请号：PCT/NL2003/000389
申请日：2003-05-26
申请人： APPLIED NANOSYSTEMS B.V. , MOLL, Gert, Nikolaas , LEENHOUTS, Cornelis, Johannes , KUIPERS, Oscar, Paul , DRIESSEN, Arnold, Jacob, Mathieu
发明人： MOLL, Gert, Nikolaas , LEENHOUTS, Cornelis, Johannes , KUIPERS, Oscar, Paul , DRIESSEN, Arnold, Jacob, Mathieu
IPC分类号： C07K14/315
CPC分类号： C12P21/02 , C07K14/315 , C07K2319/02
摘要： The invention includes a method for harvesting a polypeptide produced by a host cell, wherein the polypeptide has not undergone intra-cellular post-translational modification, such as dehydration of a serine or a threonine, and/or thioether bridge formation. The invention also includes a method for producing thioether containing peptides and dehydroalanine/dehydrobutyrine-containing peptides, wherein extracellularly thioether rings may be formed.
摘要翻译：本发明包括用于收获由宿主细胞产生的多肽的方法，其中所述多肽未经历细胞内翻译后修饰，例如丝氨酸或苏氨酸的脱水和/或硫醚桥接形成。本发明还包括制备含硫醚的肽和含有脱氢丙氨酸/脱氢丁啶的肽的方法，其中可以形成细胞外硫醚环。

2. 发明申请

WO2008130217A1 CYCLIC ANGIOTENSIN ANALOGS 审中-公开
标题翻译：循环血管生成模型
公开(公告)号：WO2008130217A1
公开(公告)日：2008-10-30
申请号：PCT/NL2006/000414
申请日：2006-08-08
申请人： APPLIED NANOSYSTEMS B.V. , HAAS, Marijke , KLUSKENS, Leonardus, Dorothea , KUIPERS, Anneke , RINK, Rick , NELEMANS, Sieger, Adriaan , MOLL, Gert, Nikolaas
发明人： HAAS, Marijke , KLUSKENS, Leonardus, Dorothea , KUIPERS, Anneke , RINK, Rick , NELEMANS, Sieger, Adriaan , MOLL, Gert, Nikolaas
IPC分类号： C07K7/14 , A61K38/08
CPC分类号： C07K7/14 , A61L31/16 , A61L2300/25
摘要： The invention relates to analogs of angiotensins, in particular to cyclised analogs having Ang(1-8) agonistic or antagonistic activity and displaying improved proteolytic resistance compared to their linear counterparts. Provided is a cyclic angiotensin peptide analog comprising a thioether-bridge linkage between the amino acids corresponding to positions Tyr4 and Pro7 in naturally occurring Angiotensin. Also provided is the use of analogs in therapy, for example hypertension.
摘要翻译：本发明涉及血管紧张素的类似物，特别是具有Ang（1-8）激动剂或拮抗活性的环化类似物，并且与其线性对应物相比显示出改善的蛋白水解抗性。本发明提供了一种环状血管紧张素肽类似物，其包含在天然存在的血管紧张素中对应于位置Tyr4和Pro7的氨基酸之间的硫醚 - 桥连接。还提供了在治疗中使用类似物，例如高血压。

3. 发明申请

WO2008018792A3 CYCLIC ANGIOTENSIN ANALOGS 审中-公开
标题翻译：循环血管紧张素类似物
公开(公告)号：WO2008018792A3
公开(公告)日：2008-04-03
申请号：PCT/NL2007050396
申请日：2007-08-07
申请人： APPLIED NANOSYSTEMS BV , STICHTING TECH WETENSCHAPP , HAAS MARIJKE , KLUSKENS LEONARDUS DOROTHEA , KUIPERS ANNEKE , RINK RICK , NELEMANS SIEGER ADRIAAN , MOLL GERT NIKOLAAS
发明人： HAAS MARIJKE , KLUSKENS LEONARDUS DOROTHEA , KUIPERS ANNEKE , RINK RICK , NELEMANS SIEGER ADRIAAN , MOLL GERT NIKOLAAS
IPC分类号： C07K7/14 , A61K38/08 , A61L31/16
CPC分类号： C07K7/14 , A61L31/16 , A61L2300/25
摘要： The invention relates to analogs of angiotensins, in particular to cyclised analogs having Ang(l-8) agonistic or antagonistic activity and to cyclised Ang(l-7) analogs with agonistic or antagonistic activity and displaying improved proteolytic resistance compared to their linear counterparts. Provided is a cyclic angiotensin peptide analog comprising a thioether-bridge linkage between the amino acids corresponding to positions Tyr 4 and Pro 7 in naturally occurring Angiotensin. Also provided is the use of analogs in therapy, for example hypertension.
摘要翻译：本发明涉及血管紧张肽类似物，特别是涉及具有Ang（1-8）激动或拮抗活性的环化类似物和具有激动或拮抗活性的环化Ang（1-7）类似物，并且与其线性对应物相比显示出改善的蛋白水解抗性。提供了一种环状血管紧张素肽类似物，其在对应于天然存在的血管紧张素中的Tyr 4和Pro 7的氨基酸之间包含硫醚 - 桥键。还提供了类似物在治疗中的用途，例如高血压。

4. 发明申请

WO03099862A8 EXPORT AND MODIFICATION OF (POLY)PEPTIDES IN THE LANTIBIOTIC WAY 审中-公开
标题翻译：（POLY）PEPTIDES在生态方式的出口和修改
公开(公告)号：WO03099862A8
公开(公告)日：2004-03-11
申请号：PCT/NL0300389
申请日：2003-05-26
申请人： APPLIED NANOSYSTEMS BV , MOLL GERT NIKOLAAS , LEENHOUTS CORNELIS JOHANNES , KUIPERS OSCAR PAUL , DRIESSEN ARNOLD JACOB MATHIEU
发明人： MOLL GERT NIKOLAAS , LEENHOUTS CORNELIS JOHANNES , KUIPERS OSCAR PAUL , DRIESSEN ARNOLD JACOB MATHIEU
IPC分类号： A61K38/14 , C07K9/00 , C07K14/315 , C12N5/06 , C12P21/02
CPC分类号： C12P21/02 , C07K14/315 , C07K2319/02
摘要： The invention includes a method for harvesting a polypeptide produced by a host cell, wherein the polypeptide has not undergone intra-cellular post-translational modification, such as dehydration of a serine or a threonine, and/or thioether bridge formation. The invention also includes a method for producing thioether containing peptides and dehydroalanine/dehydrobutyrine-containing peptides, wherein extracellularly thioether rings may be formed.
摘要翻译：本发明包括用于收获由宿主细胞产生的多肽的方法，其中所述多肽未经历细胞内翻译后修饰，例如丝氨酸或苏氨酸的脱水和/或硫醚桥接形成。本发明还包括一种生产含硫醚的肽和含有脱氢丙氨酸/脱氢丁啶的肽的方法，其中可以形成细胞外硫醚环。

5. 发明申请

WO2012070936A1 NOVEL ANGIOTENSIN TYPE 2 (AT2) RECEPTOR AGONISTS AND USES THEREOF 审中-公开
标题翻译：新型血管紧张素Ⅱ型（AT2）受体激动剂及其用途
公开(公告)号：WO2012070936A1
公开(公告)日：2012-05-31
申请号：PCT/NL2011/050793
申请日：2011-11-22
申请人： LANTHIOPEP B.V. , DE VRIES, Louwe , NELEMANS, Sieger Adriaan , RINCK, Rick , ROKS, Antonius Jacobus Marinus , MOLL, Gert Nikolaas
发明人： DE VRIES, Louwe , NELEMANS, Sieger Adriaan , RINCK, Rick , ROKS, Antonius Jacobus Marinus , MOLL, Gert Nikolaas
IPC分类号： C07K7/14
CPC分类号： C07K7/64 , A61K38/00 , A61K38/12 , A61K45/06 , C07K7/06 , A61K2300/00
摘要： The invention relates to novel pharmaceutically-useful peptides, in particular cyclic peptides that are agonists of the AngII type 2 receptor (AT2 receptor). The invention further relates to the use of such peptides as medicaments, to pharmaceutical compositions containing them, and to their production.
摘要翻译：本发明涉及新的药学上有用的肽，特别是作为AngII 2型受体（AT2受体）的激动剂的环肽。本发明还涉及这样的肽作为药物，含有它们的药物组合物及其制备的用途。

6. 发明申请

WO2010151126A1 BIOLOGICALLY PRODUCED CYCLIC AFFINITY TAGS 审中-公开
标题翻译：生物循环生物标签
公开(公告)号：WO2010151126A1
公开(公告)日：2010-12-29
申请号：PCT/NL2010/050389
申请日：2010-06-23
申请人： APPLIED NANOSYSTEMS B.V. , BOSMA, Tjibbe , KUIPERS, Anneke , RINK, Rick , MOLL, Gert Nikolaas
发明人： BOSMA, Tjibbe , KUIPERS, Anneke , RINK, Rick , MOLL, Gert Nikolaas
IPC分类号： C07K7/50
CPC分类号： C07K7/06 , C07K1/22 , C07K5/0812 , C07K5/1016 , C07K14/4703 , C12P21/02
摘要： The invention relates to novels ways of introducing an affinity tag into a protein of interest. Provided is an enzymatic method for providing a proteinaceous substance comprising a polypeptide of interest and a cyclic affinity tag, comprising the steps of: (a) providing at least one precursor proteinaceous substance, the precursor comprising said protein of interest and at least one motif of the general formula X1-Tag-X2, wherein X1 and X2 represent amino acids whose side chains can be linked enzymatically by a covalent bond; Tag is a short amino acid sequence capable of binding to a binding partner of the tag when cyclized; (b) contacting said precursor with at least one enzyme capable of forming a covalent bond between X1 and X2, thereby introducing an intramolecular ring structure comprising the Tag sequence; and (c) isolating the resulting cyclized proteinaceous substance. Also provided are proteinaceous substances obtainable thereby and the use thereof, for instance for preparing a peptide library.
摘要翻译：本发明涉及将亲和标签引入感兴趣的蛋白质的方法。本发明提供了一种用于提供包含感兴趣的多肽和环状亲和标签的蛋白质物质的酶法，其包括以下步骤：（a）提供至少一种前体蛋白质物质，所述前体蛋白质物质包含所述目的蛋白质和至少一种通式X1-Tag-X2，其中X1和X2表示其侧链可以通过共价键酶联的氨基酸; 标签是一个短的氨基酸序列，当环化时能够结合标签的结合配偶体; （b）使所述前体与能够在X 1和X 2之间形成共价键的至少一种酶接触，从而引入包含Tag序列的分子内环结构; 和（c）分离得到的环化蛋白质物质。还提供了可获得的蛋白质物质及其用途，例如用于制备肽文库。

7. 发明申请

WO2006062398A2 METHODS FOR THE PRODUCTION AND SECRETION OF MODIFIED PEPTIDES 审中-公开
标题翻译：方法的生产和分配修饰多肽
公开(公告)号：WO2006062398A2
公开(公告)日：2006-06-15
申请号：PCT/NL2005/000842
申请日：2005-12-07
申请人： Applied NanoSystems B.V. , MOLL, Gert Nikolaas , KUIPERS, Anneke , RINK, Rick , DRIESSEN, Arnold Jacob Mathieu , KUIPERS, Oscar Paul
发明人： MOLL, Gert Nikolaas , KUIPERS, Anneke , RINK, Rick , DRIESSEN, Arnold Jacob Mathieu , KUIPERS, Oscar Paul
IPC分类号： C12N15/62 , C12P21/02
CPC分类号： C12N15/625
摘要： The invention relates to the production of heterologous polypeptides in a recombinant host cell. More specifically, it relates to the production and secretion of peptides, such as biologically active peptides, that are modified by one or more lantibiotic-synthesizing enzymes. Provided is a nucleic acid construct encoding a polypeptide comprising 1) a non-lantibiotic export signal that is recognized by a non-lantibiotic export system; 2) a lantibiotic leader peptide that is recognized by at least a lantibiotic dehydratase such as LanB and, C-terminally of said export signal and said leader peptide, 3) a peptide of interest containing one or more serine or threonine residue(s) which can be posttranslationally dehydrated by said dehydratase. Also provided is a method for producing a polypeptide in a host cell, comprising providing a host cell with a nucleic acid construct according to the invention and allowing expression and secretion of the encoded polypeptide by said host cell, wherein said host cell comprises at least a dehydratase capable of modifying said encoded polypeptide and a non-lantibiotic export system capable of secreting said modified polypeptide.
摘要翻译：本发明涉及在重组宿主细胞中生产异源多肽。更具体地说，它涉及被一种或多种羊毛硫抗生素合成酶修饰的肽（例如生物活性肽）的产生和分泌。提供编码多肽的核酸构建体，其包含1）由非羊毛硫抗生素输出系统识别的非羊毛硫抗生素输出信号; 2）被至少一种羊毛硫抗生素脱水酶如LanB和所述输出信号和所述前导肽的C端识别的羊毛硫抗生素前导肽，3）一种含有一个或多个丝氨酸或苏氨酸残基的感兴趣的肽，可以通过所述脱水酶进行翻译后脱水。还提供了用于在宿主细胞中产生多肽的方法，包括向宿主细胞提供根据本发明的核酸构建体并且允许所述宿主细胞表达和分泌编码的多肽，其中所述宿主细胞包含至少一个能够修饰所述编码的多肽的脱水酶和能够分泌所述修饰的多肽的非羊毛硫抗生素输出系统。

8. 发明申请

WO2008018792A2 CYCLIC ANGIOTENSIN ANALOGS 审中-公开
公开(公告)号：WO2008018792A2
公开(公告)日：2008-02-14
申请号：PCT/NL2007/050396
申请日：2007-08-07
申请人： APPLIED NANOSYSTEMS B.V. , STICHTING VOOR DE TECHNISCHE WETENSCHAPPEN , HAAS, Marijke , KLUSKENS, Leonardus, Dorothea , KUIPERS, Anneke , RINK, Rick , NELEMANS, Sieger, Adriaan , MOLL, Gert, Nikolaas
发明人： HAAS, Marijke , KLUSKENS, Leonardus, Dorothea , KUIPERS, Anneke , RINK, Rick , NELEMANS, Sieger, Adriaan , MOLL, Gert, Nikolaas
IPC分类号： C07K7/14 , A61K38/08 , A61L31/16
CPC分类号： C07K7/14 , A61L31/16 , A61L2300/25
摘要： The invention relates to analogs of angiotensins, in particular to cyclised analogs having Ang(l-8) agonistic or antagonistic activity and to cyclised Ang(l-7) analogs with agonistic or antagonistic activity and displaying improved proteolytic resistance compared to their linear counterparts. Provided is a cyclic angiotensin peptide analog comprising a thioether-bridge linkage between the amino acids corresponding to positions Tyr 4 and Pro 7 in naturally occurring Angiotensin. Also provided is the use of analogs in therapy, for example hypertension.
摘要翻译：本发明涉及血管紧张素类似物，特别是具有Ang（1-8）激动剂或拮抗活性的环化类似物和具有激动作用或拮抗活性的环化Ang（1-7）类似物，并且与线性对应物相比显示出改善的蛋白水解抗性。本发明提供一种环状血管紧张素肽类似物，其包含在天然存在的血管紧张素中对应于位置Tyr4和Pro7的氨基酸之间的硫醚 - 桥连接。还提供了在治疗中使用类似物，例如高血压。

9. 发明申请

WO2006062398A3 METHODS FOR THE PRODUCTION AND SECRETION OF MODIFIED PEPTIDES 审中-公开
标题翻译：改性肽的生产和分泌方法
公开(公告)号：WO2006062398A3
公开(公告)日：2006-10-19
申请号：PCT/NL2005000842
申请日：2005-12-07
申请人： APPLIED NANOSYSTEMS BV , MOLL GERT NIKOLAAS , KUIPERS ANNEKE , RINK RICK , DRIESSEN ARNOLD JACOB MATHIEU , KUIPERS OSCAR PAUL
发明人： MOLL GERT NIKOLAAS , KUIPERS ANNEKE , RINK RICK , DRIESSEN ARNOLD JACOB MATHIEU , KUIPERS OSCAR PAUL
IPC分类号： C12N15/62 , C12P21/02
CPC分类号： C12N15/625
摘要： The invention relates to the production of heterologous polypeptides in a recombinant host cell. More specifically, it relates to the production and secretion of peptides, such as biologically active peptides, that are modified by one or more lantibiotic-synthesizing enzymes. Provided is a nucleic acid construct encoding a polypeptide comprising 1) a non-lantibiotic export signal that is recognized by a non-lantibiotic export system; 2) a lantibiotic leader peptide that is recognized by at least a lantibiotic dehydratase such as LanB and, C-terminally of said export signal and said leader peptide, 3) a peptide of interest containing one or more serine or threonine residue(s) which can be posttranslationally dehydrated by said dehydratase. Also provided is a method for producing a polypeptide in a host cell, comprising providing a host cell with a nucleic acid construct according to the invention and allowing expression and secretion of the encoded polypeptide by said host cell, wherein said host cell comprises at least a dehydratase capable of modifying said encoded polypeptide and a non-lantibiotic export system capable of secreting said modified polypeptide.
摘要翻译：本发明涉及在重组宿主细胞中产生异源多肽。更具体地，本发明涉及由一种或多种羊毛硫素合成酶修饰的肽（例如生物活性肽）的产生和分泌。本发明提供了编码多肽的核酸构建体，其包括1）非耐药物生物出口信号，其被非拉丁生物出口系统识别; 2）由至少一种羊毛硫抗生素脱水酶（例如LanB）和所述出口信号和所述前导肽的C-末端识别的羊毛硫素前导肽，3）感兴趣的肽含有一个或多个丝氨酸或苏氨酸残基，其中可以通过所述脱水酶进行翻译后脱水。还提供了在宿主细胞中产生多肽的方法，其包括向宿主细胞提供根据本发明的核酸构建体，并允许所述宿主细胞表达和分泌编码的多肽，其中所述宿主细胞至少包含能够修饰所述编码的多肽的脱水酶和能够分泌所述修饰的多肽的非拉链菌素出口系统。

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