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1. 发明授权

US5068314A Lipopolysaccharide-binding polypeptide 失效
标题翻译：脂多糖结合多肽
公开(公告)号：US5068314A
公开(公告)日：1991-11-26
申请号：US348487
申请日：1989-04-19
申请人： Takanori Nakamura , Sadaaki Iwanaga , Motonori Ohno , Kyosuke Miyazaki
发明人： Takanori Nakamura , Sadaaki Iwanaga , Motonori Ohno , Kyosuke Miyazaki
IPC分类号： A61K38/00 , A61P1/04 , A61P1/12 , A61P1/16 , A61P17/00 , A61P29/00 , A61P31/04 , A61P37/00 , A61P43/00 , C07K20060101 , C07K1/02 , C07K1/04 , C07K1/06 , C07K1/113 , C07K1/14 , C07K7/08 , C07K7/64 , C07K14/435 , C07K14/81
CPC分类号： C07K7/08 , A61K38/00
摘要： This invention relates to a novel polypeptide represented by the formula: ##STR1## (wherein Lys represents lysine, Trp tryptophan, Cys cystine, Phe phenylalanine, Arg arginine, Val valine, Tyr tyrosine, Gly glycine, Ile isoleucine and X a hydroxyl group or an amino group), its analogue and a method for preparing the same.The polypeptide exhibits strong affinity for lipolysaccharide, and is useful for removing endotoxin and as a therapeutic agent of bacterial infections.
摘要翻译： PCT No.PCT / JP88 / 00823 Sec。 371日期1989年8月19日 102（e）日期1989年8月19日PCT PCT 1988年8月19日PCT公布。出版物WO89 / 01492 本发明涉及由下式表示的新型多肽：其中Lys表示赖氨酸，Trp色氨酸，Cys胱氨酸，Phe苯丙氨酸，Arg精氨酸，Val缬氨酸，酪氨酸酪氨酸，Gly 甘氨酸，异亮氨酸，X为羟基或氨基），其类似物及其制备方法。该多肽对脂多糖表现出强亲和力，并且可用于除去内毒素和作为细菌感染的治疗剂。

2. 发明授权

US5416194A Polypeptide having affinity for lipopolysaccharide and method for preparing the same 失效
标题翻译：对脂多糖具有亲和力的多肽及其制备方法
公开(公告)号：US5416194A
公开(公告)日：1995-05-16
申请号：US926965
申请日：1992-08-07
申请人： Takanori Nakamura , Sadaaki Iwanaga
发明人： Takanori Nakamura , Sadaaki Iwanaga
IPC分类号： A61K38/00 , A61P1/04 , A61P1/12 , A61P1/16 , A61P17/00 , A61P29/00 , A61P31/04 , A61P37/00 , A61P43/00 , C07K20060101 , C07K1/02 , C07K1/04 , C07K1/06 , C07K1/113 , C07K1/14 , C07K7/08 , C07K7/64 , C07K14/435 , C07K14/81 , A61K31/715 , C07K5/12
CPC分类号： C07K7/08 , A61K38/00
摘要： This invention relates to a novel polypeptide represented by the formula: ##STR1## wherein Lys represents lysine, Trp tryptophan, Cys cystine, Phe phenylalanine, Arg arginine, Val valine, Tyr tyrosine, Gly glycine, Ile isoleucine and X a hydroxyl group or an amino group), its analogue and a method for preparing the same.The polypeptide exhibits strong affinity for lipopolysaccharide, and is useful for removing endotoxin and as a therapeutic agent of bacterial infections, and a method for preparing the same.
摘要翻译：本发明涉及由下式表示的新型多肽：其中Lys表示赖氨酸，Trp色氨酸，Cys胱氨酸，Phe苯丙氨酸，Arg精氨酸，Val缬氨酸，Tyr酪氨酸，Gly甘氨酸，异亮氨酸和X a羟基基团或氨基），其类似物及其制备方法。该多肽对脂多糖表现出很强的亲和性，并且可用于除去内毒素和作为细菌感染的治疗剂及其制备方法。

3. 发明授权

US5760177A Lipopolysaccharide binding protein and process for producing the same 失效
标题翻译：脂多糖结合蛋白及其制备方法
公开(公告)号：US5760177A
公开(公告)日：1998-06-02
申请号：US393058
申请日：1995-02-23
申请人： Sadaaki Iwanaga , Shunichiro Kawabata , Tetsu Saito
发明人： Sadaaki Iwanaga , Shunichiro Kawabata , Tetsu Saito
IPC分类号： A61K9/08 , A61K38/00 , C07K1/22 , C07K14/00 , C07K14/435 , G01N33/579 , G01N33/92 , A61K39/385
CPC分类号： C07K14/43509 , A61K38/00 , Y10S530/82
摘要： The invention provides a lipopolysaccharide (LPS) binding protein isolated from horseshoe crab. The LPS binding protein is isolated by (i) extracting the hemocyte membrane fraction of horseshoe crab with a polyethylene glycol ether type nonionic surface active agent in the presence of Ca ions, (ii) combining the extract with immobilized LPS under conditions that permit the LPS binding protein to bind the immobilized LPS to produce an LPS-LPS binding protein complex, and (iii) harvesting the LPS binding protein released from the complex in the presence of a chelating agent. The isolated LPS binding protein has a molecular weight of about 27,000 daltons as determined by SDS polyacrylamide gel electrophoresis and is operative to bind a lipopolysaccharide endotoxin. Accordingly, the isolated LPS binding protein can be used for detecting endotoxin and/or removing endotoxin from an injectable medicine.
摘要翻译：本发明提供从马蹄蟹分离的脂多糖（LPS）结合蛋白。通过（i）在Ca离子存在下用聚乙二醇醚型非离子表面活性剂提取鲎的血细胞膜级分，分离LPS结合蛋白，（ii）在允许LPS的条件下将提取物与固定的LPS组合结合蛋白质以结合固定的LPS以产生LPS-LPS结合蛋白复合物，和（iii）在螯合剂存在下从复合物中收获释放的LPS结合蛋白。通过SDS聚丙烯酰胺凝胶电泳测定，分离的LPS结合蛋白具有约27,000道尔顿的分子量，并且可操作地结合脂多糖内毒素。因此，分离的LPS结合蛋白可用于从可注射药物中检测内毒素和/或除去内毒素。

4. 发明授权

US6077946A DNA encoding horseshoe crab amebocyte lysate factor G subunit A 有权
标题翻译：编码鲎的细胞裂解物因子G亚基A的DNA
公开(公告)号：US6077946A
公开(公告)日：2000-06-20
申请号：US330945
申请日：1999-06-11
申请人： Sadaaki Iwanaga , Tatsushi Muta , Noriaki Seki , Toshio Oda
发明人： Sadaaki Iwanaga , Tatsushi Muta , Noriaki Seki , Toshio Oda
IPC分类号： C07K14/435 , C12N15/12 , C12N15/82 , G01N33/579 , C07H21/02 , C07H21/04
CPC分类号： G01N33/579 , C07K14/43509 , C12N15/8282
摘要： This invention relates to a DNA shown by SEQ ID No. 1 and an amino acid sequence coded by said DNA. This invention also relates to a DNA and an amino acid sequence of subunit a of (1.fwdarw.3)-.beta.-glucan sensitive factor derived from amebocytes of horseshoe crab and have potent affinity to (1.fwdarw.3)-.beta.-D-glucan in cell walls of fungi. Therefore, the invention is useful for the diagnosis of fungal diseases and as antimicrobial or eradicating agent of fungi in combination with an antifungal agent.
摘要翻译：本发明涉及SEQ ID No.1所示的DNA和由所述DNA编码的氨基酸序列。本发明还涉及来源于鲎的小单体的（1-> 3）-β-葡聚糖敏感因子亚单位a的DNA和氨基酸序列，并且对（1-> 3）-β-D- 葡聚糖在真菌的细胞壁中。因此，本发明可用于真菌疾病的诊断和与抗真菌剂组合的真菌的抗微生物剂或根除剂。

5. 发明授权

US5965725A Polypeptides, and preparation and DNA encoding thereof 失效
标题翻译：多肽，及其编码和编码DNA
公开(公告)号：US5965725A
公开(公告)日：1999-10-12
申请号：US18170
申请日：1998-02-03
申请人： Sadaaki Iwanaga , Shun-ichiro Kawabata , Tetsu Saito
发明人： Sadaaki Iwanaga , Shun-ichiro Kawabata , Tetsu Saito
IPC分类号： C12N15/09 , A61K38/00 , A61P17/00 , A61P31/04 , C07H21/04 , C07K1/20 , C07K14/435 , C12P21/02
CPC分类号： C07K14/43509 , A61K38/00 , Y10S530/857
摘要： The present invention relates to polypeptide having a primary structure of amino acid sequence shown by Sequence List Sequence No. 1 and DNA encoding for the polypeptide. The polypeptide is obtainable by following steps (1)-(3):Step (1): extracting small granule fraction of homocytes of horseshoe crab with a buffer containing protein denaturing agent and chelating agent,Step (2): subjecting said extract to reverse phase high performance liquid chromatography,Step (3): eluting by concentration gradient elution with a hydrophobic organic solvent.Also, the polypeptide is produced by chemical synthesis. The polypeptide has similar chemical structure to defensin and is useful as gargles, disinfectants, antiseptics or antimicrobials.
摘要翻译：本发明涉及具有序列表序列号1所示的氨基酸序列的一级结构的多肽和编码该多肽的DNA。通过以下步骤（1） - （3）可获得多肽：步骤（1）：用含有蛋白质变性剂和螯合剂的缓冲液提取鲎的同质异构体的小颗粒级分，步骤（2）：使所述提取物逆转阶段高效液相色谱法，步骤（3）：用疏水性有机溶剂的浓度梯度洗脱洗脱。而且，多肽是通过化学合成产生的。该多肽与防御素具有相似的化学结构，可用作漱口剂，消毒剂，防腐剂或抗微生物剂。

6. 发明授权

US5861378A Horseshoe crab hemocyte polypeptides, and preparation and DNA encoding thereof 失效
标题翻译：马蹄蟹血细胞多肽及其制备及编码DNA
公开(公告)号：US5861378A
公开(公告)日：1999-01-19
申请号：US505617
申请日：1995-07-21
申请人： Sadaaki Iwanaga , Shun-ichiro Kawabata , Tetsu Saito
发明人： Sadaaki Iwanaga , Shun-ichiro Kawabata , Tetsu Saito
IPC分类号： C12N15/09 , A61K38/00 , A61P17/00 , A61P31/04 , C07H21/04 , C07K1/20 , C07K14/435 , C12P21/02 , A61K38/17
CPC分类号： C07K14/43509 , A61K38/00 , Y10S530/857
摘要： The present invention relates to polypeptide having a primary structure of amino acid sequence shown by Sequence List Sequence No. 1 and DNA encoding for the polypeptide. The polypeptide is obtainable by following steps (1)-(3):Step (1): extracting small granule fraction of homocytes of horseshoe crab with a buffer containing protein denaturing agent and chelating agent,Step (2): subjecting said extract to reverse phase high performance liquid chromatography,Step (3): eluting by concentration gradient elution with a hydrophobic organic solvent.Also, the polypeptide is produced by chemical synthesis. The polypeptide has similar chemical structure to defensin and is useful as gargles, disinfectants, antiseptics or antimicrobials.
摘要翻译：本发明涉及具有序列表序列号1所示的氨基酸序列的一级结构的多肽和编码该多肽的DNA。通过以下步骤（1） - （3）可获得多肽：步骤（1）：用含有蛋白质变性剂和螯合剂的缓冲液提取鲎的同质异体的小颗粒级分，步骤（2）：使所述提取物逆转阶段高效液相色谱法，步骤（3）：用疏水性有机溶剂的浓度梯度洗脱洗脱。而且，多肽是通过化学合成产生的。该多肽与防御素具有相似的化学结构，可用作漱口剂，消毒剂，防腐剂或抗微生物剂。

7. 发明授权

US5795962A Horseshoe crab amebocyte lysate factor G subunit A 失效
标题翻译：马蹄蟹细胞裂解物因子G亚基A
公开(公告)号：US5795962A
公开(公告)日：1998-08-18
申请号：US392828
申请日：1995-02-28
申请人： Sadaaki Iwanaga , Tatsushi Muta , Noriaki Seki , Toshio Oda
发明人： Sadaaki Iwanaga , Tatsushi Muta , Noriaki Seki , Toshio Oda
IPC分类号： C07K14/435 , C12N15/12 , C12N15/82 , G01N33/579 , C07K14/745 , C12N9/50
CPC分类号： G01N33/579 , C07K14/43509 , C12N15/8282
摘要： This invention relates to a DNA shown by SEQ ID No. 1 and an amino acid sequence coded by said DNA. This invention also relates to a DNA and an amino acid sequence of subunit a of (1.fwdarw.3)-.beta.-D-glucan sensitive factor derived from amebocytes of horseshoe crab and have potent affinity to (1.fwdarw.3)-.beta.-D-glucan in cell walls of fungi. Therefore, the invention is useful for the diagnosis of fungal diseases and as antimicrobial or eradicating agent of fungi in combination with an antifungal agent.
摘要翻译： PCT No.PCT / JP94 / 01057 Sec。 371日期1995年2月28日 102（e）1995年2月28日PCT PCT 1994年6月29日PCT公布。公开号WO95 / 01432 日期1995年1月12日本发明涉及SEQ ID No.1所示的DNA和由所述DNA编码的氨基酸序列。本发明还涉及来源于鲎的微泡的（1-> 3）-β-D-葡聚糖敏感因子的亚基a的DNA和氨基酸序列，并且对（1-> 3）-β- 真菌细胞壁中的D-葡聚糖。因此，本发明可用于真菌疾病的诊断和与抗真菌剂组合的真菌的抗微生物剂或根除剂。

8. 发明授权

US4188264A Process for determining bacterial endotoxin and reagents used therefor 失效
标题翻译：用于确定细菌内毒素的方法和用于其的试剂
公开(公告)号：US4188264A
公开(公告)日：1980-02-12
申请号：US847582
申请日：1977-11-01
申请人： Sadaaki Iwanaga , Takashi Morita , Shin Nakamura , Kenji Takahashi , Makoto Niwa
发明人： Sadaaki Iwanaga , Takashi Morita , Shin Nakamura , Kenji Takahashi , Makoto Niwa
IPC分类号： C07K5/083 , C07K5/087 , C07K5/093 , C07K5/097 , C07K5/103 , C07K7/06 , C12Q1/34 , C12Q1/37 , G01N33/579 , G01N33/68 , G01N31/14
CPC分类号： C07K7/06 , C07K5/0804 , C07K5/0812 , C07K5/0819 , C07K5/0823 , C07K5/101 , C12Q1/37 , G01N33/579 , C12Q2337/12 , Y02P20/55 , Y10S930/28
摘要： A process for determining a bacterial endotoxin, which comprises contacting an assay sample with (A) a material selected from the group consisting of an amoebocyte lysate of horseshoe crab an a pro-clotting enzyme separated from the lysate, and (B) a peptide-type substrate of the formula (R.sub.1 --Gly--Arg--R.sub.2), wherein R.sub.1 represents a member selected from the group consisting of an L-amino acid moiety whose N-terminal is protected by a protective group, a peptide moiety consisting of an L-amino acid and protected by a protective group at its N-terminal, a D-amino acid substituted L-amino acid moiety, and a D-amino acid substituted peptide moiety consisting of an L-amino acid, and is bonded to the amino group of the glycine moiety expressed by Gly through a peptide bond; and R.sub.2 represents a moiety which is bonded to the C-terminal of an L-arginine moiety expressed by Arg through an acid amide bond and/or ester bond and can be enzymatically hydrolyzed in the presence of the material (A) and the endotoxin to liberate R.sub.2 H, and/or its mineral acid salt, and detecting the resulting R.sub.2 H in which R.sub.2 is as defined above; and the above reagent used therefor.
摘要翻译：一种确定细菌内毒素的方法，其包括使测定样品与（A）选自由鲎的变形细胞裂解物组成的组中的材料与从裂解物分离的促凝血酶接触，和（B）式（R1-Gly-Arg-R2）的底物，其中R1表示选自由N-末端被保护基保护的L-氨基酸部分的成员，由L组成的肽部分 N-氨基酸，其保护基在其N-末端，D-氨基酸取代的L-氨基酸部分和由L-氨基酸组成的D-氨基酸取代的肽部分保护，并与氨基酸连接通过肽键由Gly表示的甘氨酸部分的基团; 并且R 2表示通过酰胺键和/或酯键与Arg表示的L-精氨酸部分的C-末端键合的部分，并且可以在材料（A）和内毒素的存在下进行酶促水解释放R2H和/或其无机酸盐，并检测其中R2如上所定义的所得R2H; 和用于其的上述试剂。

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