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1. 发明授权

US08796183B2 Template fixed beta-hairpin loop mimetics and their use in phage display 有权
标题翻译：模板固定β-发夹环模拟物及其在噬菌体展示中的应用
公开(公告)号：US08796183B2
公开(公告)日：2014-08-05
申请号：US13196712
申请日：2011-08-02
申请人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Françoise Jung
发明人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Françoise Jung
IPC分类号： C40B30/04 , C07K5/00
CPC分类号： C07K1/047 , C12N15/1037 , C40B40/02
摘要： A method of screening for template-fixed β-hairpin mimetics and libraries including a plurality of these mimetics is provided. The template-fixed β-hairpin mimetics are of the following general formula: R1-Cys-Z-Cys-R2 I wherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; R1 and R2 are di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-α-amino acid.
摘要翻译：提供了一种筛选模板固定和模板模拟物的方法和包括多种这些模拟物的文库。模板固定和双螺旋模拟物具有以下通式：R1-Cys-Z-Cys-R2I，其中两个半胱氨酸残基通过二硫键桥接，从而形成环肽; R1和R2是如本文所定义的某些类型的二肽或三肽部分; 并且Z是n个氨基酸残基的链，n是4至20的整数，并且这些n个氨基酸残基中的每一个独立地衍生自任何天然存在的L-α-氨基酸。

2. 发明申请

US20110319291A1 TEMPLATE FIXED BETA-HAIRPIN LOOP MIMETICS AND THEIR USE IN PHAGE DISPLAY 有权
公开(公告)号：US20110319291A1
公开(公告)日：2011-12-29
申请号：US13196712
申请日：2011-08-02
申请人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Françoise Jung
发明人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Françoise Jung
IPC分类号： C40B30/04
CPC分类号： C07K1/047 , C12N15/1037 , C40B40/02
摘要： Template-fixed β-hairpin mimetics and libraries including a plurality of these mimetics are provided. The template-fixed β-hairpin mimetics are of the following general formula: R1-Cys-Z-Cys-R2 I wherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; R1 and R2 are di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-α-amino acid.

3. 发明授权

US08642560B2 Template fixed β-hairpin loop mimetics and their use in phage display 有权
标题翻译：模板固定β-发夹环模拟物及其在噬菌体展示中的应用
公开(公告)号：US08642560B2
公开(公告)日：2014-02-04
申请号：US13196658
申请日：2011-08-02
申请人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Françoise Jung
发明人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Françoise Jung
IPC分类号： A61K38/10 , A61K38/08
CPC分类号： C07K1/047 , C12N15/1037 , C40B40/02
摘要： Template-fixed β-hairpin mimetics and libraries including a plurality of these mimetics are provided. The template-fixed β-hairpin mimetics are of the following general formula: R1-Cys-Z-Cys-R2 I wherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; R1 and R2 are di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-α-amino acid.
摘要翻译：提供了模板固定的β-发夹模拟物和包括多个这些模拟物的文库。模板固定的β-发夹模拟物具有以下通式：R1-Cys-Z-Cys-R2I，其中两个半胱氨酸残基通过二硫键桥连，由此形成环肽; R1和R2是如本文所定义的某些类型的二肽或三肽部分; 并且Z是n个氨基酸残基的链，n是4至20的整数，并且这些n个氨基酸残基中的每一个独立地衍生自任何天然存在的L-α-氨基酸。

4. 发明申请

US20110294702A1 TEMPLATE FIXED BETA-HAIRPIN LOOP MIMETICS AND THEIR USE IN PHAGE DISPLAY 有权
标题翻译：模板固定的BETA-HAIRPIN环状物质及其在PHAGE显示中的使用
公开(公告)号：US20110294702A1
公开(公告)日：2011-12-01
申请号：US13196658
申请日：2011-08-02
申请人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Françoise Jung
发明人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Françoise Jung
IPC分类号： C40B40/10
CPC分类号： C07K1/047 , C12N15/1037 , C40B40/02
摘要： Template-fixed β-hairpin mimetics and libraries including a plurality of these mimetics are provided. The template-fixed β-hairpin mimetics are of the following general formula: R1-Cys-Z-Cys-R2 I wherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; R1 and R2 are di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-α-amino acid.
摘要翻译：提供了模板固定模板和包含多个这些模拟物的文库。模板固定和双螺旋模拟物具有以下通式：R1-Cys-Z-Cys-R2I，其中两个半胱氨酸残基通过二硫键桥接，从而形成环肽; R1和R2是如本文所定义的某些类型的二肽或三肽部分; 并且Z是n个氨基酸残基的链，n是4至20的整数，并且这些n个氨基酸残基中的每一个独立地衍生自任何天然存在的L-α-氨基酸。

5. 发明授权

US07994118B2 Template fixed beta-hairpin loop mimetics and their use in phage display 有权
标题翻译：模板固定β-发夹环模拟物及其在噬菌体展示中的应用
公开(公告)号：US07994118B2
公开(公告)日：2011-08-09
申请号：US10579104
申请日：2003-11-15
申请人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Françoise Jung
发明人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Françoise Jung
IPC分类号： A61K38/04 , A61K38/12
CPC分类号： C07K1/047 , C12N15/1037 , C40B40/02
摘要： Template-fixed β-hairpin mimetics and libraries including a plurality of these mimetics are provided. The template-fixed β-hairpin mimetics are of the following general formula: R1-Cys-Z-Cys-R2 (I) wherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; R1 and R2 are di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-α-amino acid.
摘要翻译：提供了模板固定模板和包含多个这些模拟物的文库。模板固定和模板模拟物具有以下通式：R1-Cys-Z-Cys-R2（I），其中两个半胱氨酸残基用二硫键桥连，从而形成环肽; R1和R2是如本文所定义的某些类型的二肽或三肽部分; 并且Z是n个氨基酸残基的链，n是4至20的整数，并且这些n个氨基酸残基中的每一个独立地衍生自任何天然存在的L-α-氨基酸。

6. 发明申请

US20090118134A1 Template Fixed Beta-Hairpin Loop Mimetics and Their Use in Phage Display 有权
标题翻译：模板固定β-发夹环模拟物及其在噬菌体展示中的应用
公开(公告)号：US20090118134A1
公开(公告)日：2009-05-07
申请号：US10579104
申请日：2003-11-15
申请人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Francoise Jung
发明人： Jan Wim Vrijbloed , Daniel Obrecht , Sergio Locurio , Frank Otto Gombert , Christian Ludin , Francoise Jung
IPC分类号： C40B30/04 , C07K7/00 , C40B40/10 , C40B40/02
CPC分类号： C07K1/047 , C12N15/1037 , C40B40/02
摘要： Template-fixed β-hairpin mime tics of the general formula R1-Cys-Z-Cys-R2 (1) wherein the two Cys residues are bridged by a disulfide bond thereby forming a cyclic peptide; R1 and R2 are preferably Glu-Thr and Thr-Lys; or Lys-Thr and Thr-Glu; or Thr-Glu and Lys-Thr, or Thr-Lys and Glu-Thr; or Leu-Glu and Lys-Val; or Val-Lys and Glu-Leu; or Glu-Leu and Val-Lys; or Lys-Leu and Val-Glu; or Asn-Gly and Lys-Val; or Val-Gly and Lys-Asn; or Gly-Asn and Val-Lys; or Gly-Val and Asn-Lys; or Gly-Gly and Gly-Gly; or Glu-Leu-Lys and Glu-Val-Lys; or Lys-Val-Glu and Lys-Leu-Glu; or Leu-Glu-Lys and Glu-Lys-Val; or Val-Lys-Glu and Lys-Glu-Leu; or Glu-Lys-Leu and Val-Glu-Lys; or Lys-Glu-Val and Leu-Lys-Glu; or Lys-Glu-Leu and Val-Lys-Glu; or Glu-Lys-Val and Leu-Glu-Lys; or Lys-Val-Gly and Gly-Leu-Glu; or Glu-Leu-Gly and Gly-Val-Lys; or Val-Lys-Gly and Gly-Glu-Leu; or Leu-Glu-Gly and Gly-Lys-Val; or Val-Gly-Lys and Glu-Gly-Leu; or Leu-Gly-Glu and Lys-Gly-Val; or Gly-Gly-Gly and Gly-Gly-Gly; and Z is a chain of n amino acid residues with n being an integer form 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-α-amino acid are provided. Libraries comprising a plurality of these templates can be used for the construction of phage display derived template-fixed β-hairpin mimetics generating phage display libraries with very high binding constants to targets, thus combining the advantage of screening of large phage display derived template-fixed β-hairpin libraries which in turn considerably facilitates structure-activity studies, and hence the discovery of new molecules with potent activities and with novel selectivities towards different types of targets.
摘要翻译：通式R1-Cys-Z-Cys-R2（1）的模板固定β-发夹制剂，其中两个Cys残基用二硫键桥接，从而形成环肽; R1和R2优选为Glu-Thr和Thr-Lys; 或Lys-Thr和Thr-Glu; 或Thr-Glu和Lys-Thr，或Thr-Lys和Glu-Thr; 或Leu-Glu和Lys-Val; 或Val-Lys和Glu-Leu; 或Glu-Leu和Val-Lys; 或Lys-Leu和Val-Glu; 或Asn-Gly和Lys-Val; 或Val-Gly和Lys-Asn; 或Gly-Asn和Val-Lys; 或Gly-Val和Asn-Lys; 或Gly-Gly和Gly-Gly; 或Glu-Leu-Lys和Glu-Val-Lys; 或Lys-Val-Glu和Lys-Leu-Glu; 或Leu-Glu-Lys和Glu-Lys-Val; 或Val-Lys-Glu和Lys-Glu-Leu; 或Glu-Lys-Leu和Val-Glu-Lys; 或Lys-Glu-Val和Leu-Lys-Glu; 或Lys-Glu-Leu和Val-Lys-Glu; 或Glu-Lys-Val和Leu-Glu-Lys; 或Lys-Val-Gly和Gly-Leu-Glu; 或Glu-Leu-Gly和Gly-Val-Lys; 或Val-Lys-Gly和Gly-Glu-Leu; 或Leu-Glu-Gly和Gly-Lys-Val; 或Val-Gly-Lys和Glu-Gly-Leu; 或Leu-Gly-Glu和Lys-Gly-Val; 或Gly-Gly-Gly和Gly-Gly-Gly; 并且Z是n个氨基酸残基的链，n是4至20的整数，并且这些n个氨基酸残基中的每一个独立地衍生自任何天然存在的L-α-氨基酸。包含多个这些模板的文库可用于构建噬菌体展示衍生的模板固定的β-发夹模拟物，其产生具有非常高的结合常数的靶标的噬菌体展示文库，因此结合筛选大噬菌体展示衍生模板固定的优点 β-发夹文库反过来极大地促进结构活性研究，从而发现具有有效活性和对不同类型靶标具有新选择性的新分子。

7. 发明授权

US07855179B2 Template-fixed peptidomimetics with antimicrobial activity 有权
标题翻译：具有抗菌活性的模板固定肽模拟物
公开(公告)号：US07855179B2
公开(公告)日：2010-12-21
申请号：US10530335
申请日：2002-10-02
申请人： Jan Wim Vrijbloed , Daniel Obrecht , John Anthony Robinson , Sergio Locurio , Frank Gombert , Christian Ludin , Alexander Lederer , Shivaprasad Shankaramma
发明人： Jan Wim Vrijbloed , Daniel Obrecht , John Anthony Robinson , Sergio Locurio , Frank Gombert , Christian Ludin , Alexander Lederer , Shivaprasad Shankaramma
IPC分类号： A61K38/10 , C07K7/08 , C07K1/36
CPC分类号： C07K7/08 , A61K38/00 , C07K7/06 , C07K7/64 , C07K14/001
摘要： Template-fixed β-hairpin peptidomimetics of the general formula (I), wherein Z is a template-fixed chain of 12 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly or Pro, or of certain types, at least one of these residues being of the type of N-substituted glycines, which types, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to inhibit the growth of or to kill microorganisms. They can be used as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials or as medicaments to treat or prevent infections. These β-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.
摘要翻译：通式（I）的模板固定型和半乳糖肽模拟物，其中Z是12个α-氨基酸残基的模板固定链，其取决于其在链中的位置（从N-末端氨基酸开始计数）是Gly或Pro，或某些类型，这些残基中的至少一种是N-取代的甘氨酸类型，其类型作为上述式中的剩余符号在说明书和权利要求书中定义，并且盐具有抑制微生物生长或杀死微生物的性质。它们可以用作食品，化妆品，药物或其他含营养材料的消毒剂，或用作治疗或预防感染的药物。这些和平滑肽模拟物可以通过基于混合固相和溶液相合成策略的方法制造。

8. 发明申请

US20070054840A1 Template-fixed peptidomimetics with antimicrobial activity 有权
标题翻译：具有抗菌活性的模板固定肽模拟物
公开(公告)号：US20070054840A1
公开(公告)日：2007-03-08
申请号：US10530335
申请日：2002-10-02
申请人： Jan Vrijbloed , Daniel Obrecht , John Robinson , Sergio Locurio , Frank Gombert , Christian Ludin , Alexander Lederer , Shivaprasad Shankaramma
发明人： Jan Vrijbloed , Daniel Obrecht , John Robinson , Sergio Locurio , Frank Gombert , Christian Ludin , Alexander Lederer , Shivaprasad Shankaramma
IPC分类号： A61K38/12 , C07K7/60
CPC分类号： C07K7/08 , A61K38/00 , C07K7/06 , C07K7/64 , C07K14/001
摘要： Template-fixed β-hairpin peptidomimetics of the general formula (I), wherein Z is a template-fixed chain of 12 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly or Pro, or of certain types, at least one of these residues being of the type of N-substituted glycines, which types, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to inhibit the growth of or to kill microorganisms. They can be used as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials or as medicaments to treat or prevent infections. These β-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.
摘要翻译：通式（I）的模板固定的β-发夹肽模拟物，其中Z是12个α-氨基酸残基的模板固定链，其取决于其在链中的位置（从N-末端氨基酸开始计数）是Gly或Pro，或某些类型，这些残基中的至少一种是N-取代的甘氨酸类型，其类型作为上述式中的其余符号在说明书和权利要求书中定义，以及其盐具有抑制微生物生长或杀死微生物的性质。它们可以用作食品，化妆品，药物或其他含营养材料的消毒剂，或用作治疗或预防感染的药物。这些β-发夹肽模拟物可以通过基于混合固相和溶液相合成策略的方法制备。

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