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1. 发明授权

US06653442B1 Protegrins 失效
标题翻译： Protegrin
公开(公告)号：US06653442B1
公开(公告)日：2003-11-25
申请号：US09385328
申请日：1999-08-30
申请人： Conway C. Chang , Chee L. Gu , Jie Chen , Deborah A. Steinberg , Robert I. Lehrer , Sylvia S. L. Harwig , Vladimir N. Kokryakov
发明人： Conway C. Chang , Chee L. Gu , Jie Chen , Deborah A. Steinberg , Robert I. Lehrer , Sylvia S. L. Harwig , Vladimir N. Kokryakov
IPC分类号： A61K3804
CPC分类号： C07K7/08 , A01N63/02 , A61K38/00 , C07K16/18
摘要： Peptide-based compounds containing four invariant cysteine residues which have been optionally oxidized to contain two intramolecular disulfide bonds, or modified forms where the cysteines are replaced are useful as preservatives and in preventing, treating, or ameliorating viral or microbial infection in animals and plants, and in inactivating endotoxin.
摘要翻译：含有四个不变半胱氨酸残基的基于肽的化合物，其被任选地氧化成含有两个分子内二硫键，或其中替代半胱氨酸的修饰形式可用作防腐剂，并且用于预防，治疗或改善动物和植物中的病毒或微生物感染，并灭活内毒素。

2. 再颁专利

USRE38828E1 Parevins and tachytegrins 有权
标题翻译：派克宁和速激肽
公开(公告)号：USRE38828E1
公开(公告)日：2005-10-11
申请号：US10255011
申请日：2002-09-24
申请人： Robert I. Lehrer , Sylvia S. L. Harwig , Conway C. Chang , Chee L. Gu
发明人： Robert I. Lehrer , Sylvia S. L. Harwig , Conway C. Chang , Chee L. Gu
IPC分类号： A01N37/46 , A61K38/00 , A61L12/14 , C07K7/08 , A61K38/10
CPC分类号： C07K7/08 , A01N37/46 , A61K38/00 , A61L12/14
摘要： The present invention provides a new class of broad-spectrum antimicrobial peptides effective against a wide variety of microbes, including bacteria, viruses, retroviruses, fungi, yeast and protozoa.
摘要翻译：本发明提供了对各种微生物（包括细菌，病毒，逆转录病毒，真菌，酵母和原生动物）有效的一类广谱抗菌肽。

3. 发明授权

US06307016B1 Parevins and tachytegrins 有权
标题翻译：派克宁和速激肽
公开(公告)号：US06307016B1
公开(公告)日：2001-10-23
申请号：US09128344
申请日：1998-08-03
申请人： Robert I. Lehrer , Sylvia S. L. Harwig , Conway C. Chang , Chee L. Gu
发明人： Robert I. Lehrer , Sylvia S. L. Harwig , Conway C. Chang , Chee L. Gu
IPC分类号： A61K3810
CPC分类号： C07K7/08 , A01N37/46 , A61K38/00 , A61L12/14 , Y02A50/473
摘要： The present invention provides a new class of broad-spectrum antimicrobial peptides effective against a wide variety of microbes, including bacteria, viruses, retroviruses, fungi, yeast and protozoa.
摘要翻译：本发明提供了对各种微生物有效的新一类的广谱抗菌肽，包括细菌，病毒，逆转录病毒，真菌，酵母和原生动物。

4. 发明授权

US6159936A Compositions and methods for treating and preventing microbial and viral infections 有权
标题翻译：用于治疗和预防微生物和病毒感染的组合物和方法
公开(公告)号：US6159936A
公开(公告)日：2000-12-12
申请号：US128345
申请日：1998-08-03
申请人： Robert I. Lehrer , Sylvia S. L. Harwig , Vladimir N. Kokryakov
发明人： Robert I. Lehrer , Sylvia S. L. Harwig , Vladimir N. Kokryakov
IPC分类号： A01N63/02 , A61K38/00 , C07K7/08 , C07K16/18 , C12N15/12 , C12P21/04 , A61K38/04 , C07K7/00 , C12P21/02
CPC分类号： C07K7/08 , A01N63/02 , A61K38/00 , C07K16/18 , Y02A50/473 , Y02A50/481
摘要： Peptide-based compounds containing four invariant cysteine residues which have been optionally oxidized to contain two intramolecular disulfide bonds, or modified forms where the cysteines are replaced are useful as preservatives and in preventing, treating, or ameliorating viral or microbial infection in animals and plants, and in inactivating endotoxin. These compounds, in one embodiment, are of the formula:A.sub.1 --A.sub.2 --A.sub.3 --A.sub.4 --A.sub.5 --A.sub.6 --A.sub.7 --A.sub.8 --A.sub.9 --A.sub.10 --A.sub.11 --A.sub.12 --A.sub.13 --A.sub.14 --A.sub.15 --A.sub.16 --(A.sub.17 --A.sub.18) (1)and the N-terminal acylated and/or C-terminal amidated or esterified forms thereof, which is either in the optionally --SH stablizied linear or in a cystine-bridged formwherein each of A.sub.1 and A.sub.9 is independently a basic amino acid;each of A.sub.2 and A.sub.3 is independently a small amino acid;each of A.sub.5, A.sub.7, A.sub.12, A.sub.14 and A.sub.16 is independently a hydrophobic amino acid;A.sub.4 is a basic or a small amino acid;A.sub.10 is a basic or a small amino acid or is proline;A.sub.11 is a basic or hydrophobic amino acid;A.sub.17 is not present or, if present, is a small amino acid;A.sub.18 is not present or, if present, is a basic amino acid; or amodified form of formula (1) and the N-terminal acylated and/or C-terminal amidated or esterified forms thereof wherein each of 1-4 cysteines is independently replaced by a hydrophobic amino acid or a small amino acid.
摘要翻译：含有四个不变半胱氨酸残基的基于肽的化合物，其被任选地氧化成含有两个分子内二硫键，或其中替代半胱氨酸的修饰形式可用作防腐剂，并且用于预防，治疗或改善动物和植物中的病毒或微生物感染，并灭活内毒素。这些化合物在一个实施方案中具有下式：A1-A2-A3-A4-A5-A6-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-（A17-A18）（ 1）和其N-末端酰化和/或C末端酰胺化或酯化形式，其以任选-SH稳定的线性或胱氨酸桥接形式，其中A1和A9各自独立地为碱性氨基酸; A2和A3各自独立地是小氨基酸; A5，A7，A12，A14和A16各自独立地是疏水性氨基酸; A4是碱性或小氨基酸; A10是碱性或小氨基酸，或是脯氨酸; A11是碱性或疏水性氨基酸; A17不存在，或者如果存在，则是小氨基酸; A18不存在，或者如果存在，则是碱性氨基酸; 或式（1）的修饰形式和其N-末端酰化和/或C-末端酰胺化或酯化形式，其中1-4个半胱氨酸中的每一个独立地被疏水性氨基酸或小氨基酸替代。

5. 发明授权

US5464823A Mammalian antibiotic peptides 失效
标题翻译：哺乳动物抗生素肽
公开(公告)号：US5464823A
公开(公告)日：1995-11-07
申请号：US95769
申请日：1993-07-26
申请人： Robert I. Lehrer , Vladimir N. Kokryakov , Sylvia S. L. Harwig
发明人： Robert I. Lehrer , Vladimir N. Kokryakov , Sylvia S. L. Harwig
IPC分类号： A01N63/02 , A61K38/00 , C07K7/08 , C07K16/18 , C12N15/12 , C07K7/00 , A61K38/10
CPC分类号： C07K7/08 , A01N63/02 , C07K16/18 , A61K38/00
摘要： Peptide-based compounds containing four invariant cysteine residues which have been oxidized to obtain two intramolecular disulfide bonds are useful as preservatives and in preventing, treating, or ameliorating viral or microbial infection in animals and plants. These compounds, in one embodiment, are of the formula:A.sub.1 -A.sub.2 -A.sub.3 -A.sub.4 -A.sub.5 -C-A.sub.7 -C-A.sub.9 -A.sub.10 -A.sub.11 -A.sub.12 -C-A.sub.14 -C-A.sub.16 -(A.sub.17 -A.sub.18)(1) (SEQ ID NO:4)and the N-terminal acylated, C-terminal amidated or esterified and the cystine-bridged forms thereofwherein A.sub.1, A.sub.9, A.sub.10 and A.sub.11 are basic amino acids;A.sub.2 and A.sub.3 are small amino acids;A.sub.5, A.sub.7, A.sub.12, A.sub.14 and A.sub.16 are hydrophobic amino acids; andA.sub.4 is a basic or a small amino acid;A.sub.17 is not present or, if present, is a small amino acid;A.sub.18 is not present or, if present, is a basic amino acid.
摘要翻译：含有四个不变半胱氨酸残基的已经氧化得到两个分子内二硫键的基于化合物的化合物可用作防腐剂，并用于预防，治疗或改善动物和植物中的病毒或微生物感染。在一个实施方案中，这些化合物具有下式：A1-A2-A3-A4-A5-C-A7-C-A9-A10-A11-A12-C-A14-C-A16-（A17-A18）（ 1）（SEQ ID NO：4）和N-末端酰化，C-末端酰胺化或酯化，并且其中A 1，A 9，A 10和A 11是胱氨酸桥接形式是碱性氨基酸; A2和A3是小氨基酸; A5，A7，A12，A14和A16是疏水性氨基酸; A4是碱性或小氨基酸; A17不存在，或者如果存在，则是小氨基酸; A18不存在，或者如果存在，是碱性氨基酸。

6. 发明授权

US5804553A Prophenins - antibiotic peptides 失效
标题翻译：酚类抗生素肽
公开(公告)号：US5804553A
公开(公告)日：1998-09-08
申请号：US222798
申请日：1994-04-05
申请人： Vladimir N. Kokryakov , Sylvia S. L. Harwig , Robert I. Lehrer
发明人： Vladimir N. Kokryakov , Sylvia S. L. Harwig , Robert I. Lehrer
IPC分类号： A01N63/02 , C07K14/47 , C12N15/82 , A61K38/17 , A61K38/08
CPC分类号： C12N15/8279 , A01N63/02 , C07K14/47 , C07K2317/24
摘要： Peptide-based compounds containing multiple proline residues are useful as preservatives and in preventing, treating, or ameliorating microbial infection, especially Gram-negative bacterial infection in animals and plants, in treating conditions characterized by the presence of LPS. These compounds are of the formula ##STR1## including the N-terminal acylated and/or C-terminal amidated or esterified forms thereof wherein each of A.sub.1, A.sub.5, A.sub.10, A.sub.14 and A.sub.20 is independently Ala, Gly or Ser; each of A.sub.2, A.sub.4, A.sub.7, A.sub.9, A.sub.11, A.sub.12, A.sub.13, A.sub.16, A.sub.17, A.sub.19 and A.sub.22 is independently a hydrophobic amino acid selected from the group consisting of Ile, Leu, Val, Phe and Met; each of A.sub.3 and A.sub.8 is independently a neutral polar amino acid selected from Asn and Gln or is a hydrophobic amino acid selected from the group consisting of Ile, Leu, Val, Phe and Met; each of A.sub.6, A.sub.18 and A.sub.21 is independently a basic amino acid selected from Arg, Lys, and Har; and wherein A.sub.15 is Trp or a basic amino acid selected from Lys, Arg and Har; wherein n is an integer of 1-6; and the antimicrobial or LPS-binding fragments thereof. Recombinant materials for the production of these peptides are also disclosed.
摘要翻译：含有多个脯氨酸残基的基于肽的化合物可用作防腐剂，并且用于预防，治疗或改善动物和植物中的微生物感染，特别是革兰氏阴性细菌感染，治疗以LPS存在为特征的病症。这些化合物具有式A1（A2 PPP A3 A4 P A5 P A6）n（1）A7 PPP A8 A9 P A10 PP A11 PPP A12A13 P A14 P A15 A16 PPPPP A17A18 PPP A19A20 PP A21A22 P，包括N-末端酰化和 /或C末端氨基化或酯化形式，其中A1，A5，A10，A14和A20各自独立地为Ala，Gly或Ser; A2，A4，A7，A9，A11，A12，A13，A16，A17，A19和A22各自独立地是选自由Ile，Leu，Val，Phe和Met组成的组的疏水性氨基酸; A3和A8各自独立地是选自Asn和Gln的中性极性氨基酸，或者是选自由Ile，Leu，Val，Phe和Met组成的组的疏水性氨基酸; A6，A18和A21各自独立地是选自Arg，Lys和Har的碱性氨基酸; 并且其中A15是Trp或选自Lys，Arg和Har的碱性氨基酸; 其中n为1-6的整数; 和其抗微生物或LPS结合片段。还公开了用于生产这些肽的重组材料。

7. 发明授权

US5635594A Gallinacins - antibiotic peptides 失效
标题翻译：加利诺嗪 - 抗生素肽
公开(公告)号：US5635594A
公开(公告)日：1997-06-03
申请号：US212236
申请日：1994-03-11
申请人： Robert I. Lehrer , Vladimir N. Kokryakov , Sylvia S. L. Harwig
发明人： Robert I. Lehrer , Vladimir N. Kokryakov , Sylvia S. L. Harwig
IPC分类号： A01N63/02 , A61K38/00 , C07K14/465 , C12N15/82 , C07K14/435 , A61K38/17
CPC分类号： A01N63/02 , C07K14/465 , C12N15/8281 , C12N15/8282 , A61K38/00 , Y10S530/827 , Y10S530/83
摘要： Peptide-based compounds containing six invariant cysteine residues are useful as preservatives and in preventing, treating, or ameliorating microbial infection in animals and plants. These compounds are of the formulas: ##STR1## wherein each B.sub.i is a basic amino acid and the N-terminal acylated and/or C-terminal amidated or esterified forms thereof, either in optionally --SH stabilized linear or in cystine-bridged form.
摘要翻译：含有六个不变半胱氨酸残基的基于肽的化合物可用作防腐剂并用于预防，治疗或改善动物和植物中的微生物感染。这些化合物具有下式：其中每个Bi是碱性氨基酸，其N-末端酰化和/或C末端酰胺化或酯化形式，任选-SH稳定化的线性或胱氨酸曲线形式。

8. 发明授权

US5804558A Protegrins 失效
标题翻译： Protegrin
公开(公告)号：US5804558A
公开(公告)日：1998-09-08
申请号：US499523
申请日：1995-07-07
申请人： Robert I. Lehrer , Sylvia S. L. Harwig , Vladimir N. Kokryakov
发明人： Robert I. Lehrer , Sylvia S. L. Harwig , Vladimir N. Kokryakov
IPC分类号： C12N15/09 , A01N63/02 , A61K38/00 , A61P31/04 , A61P31/12 , C07K7/08 , C07K16/18 , C12N15/12 , C12P21/02 , A61K38/04 , A01N25/00 , C12N15/13
CPC分类号： C07K7/08 , A01N63/02 , C07K16/18 , A61K38/00
摘要： Peptide-based compounds containing four invariant cycteine residues which have been optionally oxidized to contain two intramolecular disulfide bonds, or modified forms where the cysteines are replaced are useful as preservatives and in preventing, treating, or ameliorating viral or microbial infection in animals and plants, and in inactivating endotoxin. These compounds, in one embodiment, are of the formula: ##STR1## and the N-terminal acylated and/or C-terminal amidated or esterified forms thereof, which is either in the optionally -SH stabilized linear or in a cystine-bridged form wherein each of A.sub.1 and A.sub.9 is independently a basic amino acid; each of A.sub.2 and A.sub.3 is independently a small amino acid; each of A.sub.5, A.sub.7, A.sub.12, A.sub.14 and A.sub.16 is independently a hydrophobic amino acid; A.sub.4 is a basic or a small amino acid; A.sub.10 is a basic or a small amino acid or is proline; A.sub.11 is a basic or a hydrophobic amino acid; A.sub.17 is not present or, if present, is a small amino acid; A.sub.18, is not present or, if present, is a basic amino acid; or a modified form of formula (1) and the N-terminal acylated and/or C-terminal amidated or esterified forms thereof wherein each of 1-4 cysteines is independently replaced by a hydrophobic amino acid or a small amino gacid.
摘要翻译：含有四个不变的cycteine残基的肽基化合物，其被任选地氧化成含有两个分子内二硫键，或其中替代半胱氨酸的修饰形式可用作防腐剂，并且可用于预防，治疗或改善动物和植物中的病毒或微生物感染，并灭活内毒素。在一个实施方案中，这些化合物具有下式：A1A2A3A4A5C6A7C8A9A10（1）A11A12C13A14C15A16（A17A18）及其N-末端酰化和/或C末端酰胺化或酯化形式，其任意为-SH稳定的线性或胱氨酸桥接形式，其中A1和A9各自独立地是碱性氨基酸; A2和A3各自独立地是小氨基酸; A5，A7，A12，A14和A16各自独立地是疏水性氨基酸; A4是碱性或小氨基酸; A10是碱性或小氨基酸，或是脯氨酸; A11是碱性或疏水性氨基酸; A17不存在，或者如果存在，则是小氨基酸; A18不存在，或者如果存在，则是碱性氨基酸; 或式（1）的修饰形式和其N-末端酰化和/或C末端酰胺化或酯化形式，其中1-4个半胱氨酸中的每一个独立地被疏水性氨基酸或小氨基酸形成。

9. 发明授权

US5693486A DNA sequences encoding protegrins and protegrin analogs and their use in recombinant methods of producing protegrins 失效
标题翻译：编码前整合素和整合蛋白类似物的DNA序列及其在重组生成原蛋白的方法中的应用
公开(公告)号：US5693486A
公开(公告)日：1997-12-02
申请号：US182483
申请日：1994-01-13
申请人： Robert I. Lehrer , Vladimir N. Kokryakov , Sylvia S. L. Harwig
发明人： Robert I. Lehrer , Vladimir N. Kokryakov , Sylvia S. L. Harwig
IPC分类号： A01N63/02 , A61K38/00 , C07K7/08 , C07K16/18 , C12N15/12 , C07K7/00 , C12N15/70
CPC分类号： C07K7/08 , A01N63/02 , C07K16/18 , A61K38/00
摘要： Peptide-based compounds containing four invariant cysteine residues which have been optionally oxidized to contain two intramolecular disulfide bonds, or modified forms where the cysteines are replaced, are useful as preservatives and in preventing, treating, or ameliorating viral or microbial infection in animals and plants, and in inactivating endotoxin. These compounds, in one embodiment, are of the formula: A.sub.1 -A.sub.2 -A.sub.3 -A.sub.4 -A.sub.5 -C-A.sub.7 -C-A.sub.9 -A.sub.10 -A.sub.11 -A.sub.12 -C-A.sub.14 -C-A.sub.16 -(A.sub.17 -A.sub.18)(1)(SEQ ID NO:1) and the N-terminal acylated and/or C-terminal amidated or esterified forms thereof, either in optionally --SH stabilized linear or in cystine-bridged form wherein A.sub.1, A.sub.9, A.sub.10, and A.sub.11 are basic amino acids; A.sub.2 and A.sub.3 are small amino acids; A.sub.5, A.sub.7, A.sub.12, A.sub.14 and A.sub.16 are hydrophobic amino acids; and A.sub.4 is a basic or a small amino acid; A.sub.17 is not present or, if present, is a small amino acid; A.sub.18 is not present or, if present, is a basic amino acid, and modified form of formula (1) SEQ ID NO:1) wherein each of 1-4 cysteines is independently replaced by a hydrophobic amino acid or a small amino acid.
摘要翻译：含有四个不变半胱氨酸残基的基于肽的化合物，其被任选地氧化成含有两个分子内二硫键，或其中替代半胱氨酸的修饰形式可用作防腐剂，并且用于预防，治疗或改善动物和植物中的病毒或微生物感染，并灭活内毒素。在一个实施方案中，这些化合物具有下式：A1-A2-A3-A4-A5-C-A7-C-A9-A10-A11-A12-C-A14-C-A16-（A17-A18）（ 1）（SEQ ID NO：1）和N-末端酰化和/或C末端酰胺化或酯化形式，其任选-SH稳定的线性或胱氨酸桥接形式，其中A1，A9，A10和A11为碱性氨基酸; A2和A3是小氨基酸; A5，A7，A12，A14和A16是疏水性氨基酸; A4是碱性或小氨基酸; A17不存在，或者如果存在，则是小氨基酸; A18不存在，或者如果存在，是碱性氨基酸，和式（1）SEQ ID NO：1）的修饰形式，其中1-4个半胱氨酸中的每一个独立地被疏水性氨基酸或小氨基酸替代。

10. 发明授权

US5633229A Method of using prophenins-antibiotic peptides 失效
标题翻译：使用丙苯霉素 - 抗生素肽的方法
公开(公告)号：US5633229A
公开(公告)日：1997-05-27
申请号：US487359
申请日：1995-06-07
申请人： Vladimir N. Kokryakov , Sylvia S. L. Harwig , Robert I. Lehrer
发明人： Vladimir N. Kokryakov , Sylvia S. L. Harwig , Robert I. Lehrer
IPC分类号： A01N63/02 , C07K14/47 , C12N15/82 , A61K38/17 , A61K38/08
CPC分类号： C12N15/8279 , A01N63/02 , C07K14/47 , C07K2317/24
摘要： Peptide-based compounds containing multiple proline residues are useful as preservatives and in preventing, treating, or ameliorating microbial infection, especially Gram-negative bacterial infection in animals and plants, in treating conditions characterized by the presence of LPS. These compounds are of the formula ##STR1## including the N-terminal acylated and/or C-terminal amidated or esterified forms thereofwherein each of A.sub.1, A.sub.5, A.sub.1O, A.sub.14 and A.sub.20 is independently Ala, Gly or Ser;each of A.sub.2, A.sub.4, A.sub.7, A.sub.9, A.sub.11, A.sub.12, A.sub.13, A.sub.16, A.sub.17, A.sub.19 and A.sub.22 is independently a hydrophobic amino acid selected from the group consisting of Ile, Leu, Val, Phe and Met;each of A.sub.3 and A.sub.8 is independently a neutral polar amino acid selected from Asn and Gln or is a hydrophobic amino acid selected from the group consisting of Ile, Leu, Val, Phe and Met;each of A.sub.6, A.sub.18 and A.sub.21 is independently a basic amino acid selected from Arg, Lys, and Har; andwherein A.sub.15 is Trp or a basic amino acid selected from Lys, Arg and Har;wherein n is an integer of 1-6; and the antimicrobial or LPS-binding fragments thereof. Recombinant materials for the production of these peptides are also disclosed.
摘要翻译：含有多个脯氨酸残基的基于肽的化合物可用作防腐剂，并且用于预防，治疗或改善动物和植物中的微生物感染，特别是革兰氏阴性细菌感染，治疗以LPS存在为特征的病症。这些化合物具有下式（1），其包括N-末端酰化和/或C-末端酰胺化或酯化形式，其中A1，A5，A1O，A14和A20各自独立地为Ala，Gly或Ser; A2，A4，A7，A9，A11，A12，A13，A16，A17，A19和A22各自独立地是选自由Ile，Leu，Val，Phe和Met组成的组的疏水性氨基酸; A3和A8各自独立地是选自Asn和Gln的中性极性氨基酸，或者是选自由Ile，Leu，Val，Phe和Met组成的组的疏水性氨基酸; A6，A18和A21各自独立地是选自Arg，Lys和Har的碱性氨基酸; 并且其中A15是Trp或选自Lys，Arg和Har的碱性氨基酸; 其中n为1-6的整数; 和其抗微生物或LPS结合片段。还公开了用于生产这些肽的重组材料。

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