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公开(公告)号:US07459427B2
公开(公告)日:2008-12-02
申请号:US11214371
申请日:2005-08-29
申请人: Wylie W. Vale, Jr. , Kathy A. Lewis , Marilyn H. Perrin , Koichi S. Kunitake , Jean E. Rivier , Jozsef Gulyas
发明人: Wylie W. Vale, Jr. , Kathy A. Lewis , Marilyn H. Perrin , Koichi S. Kunitake , Jean E. Rivier , Jozsef Gulyas
IPC分类号: C07K14/00
CPC分类号: A61K38/2228 , A61K38/00 , C07K14/57509 , C07K14/695
摘要: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2α or β. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.
摘要翻译: 公众人类基因组数据库的搜索确定了人类EST,GenBank登录号AW293249,其与已知的河豚urocortin序列具有高同源性。 从人类基因组DNA扩增全长序列并进行测序。 新序列与人尿皮质素I和尿皮质素II的序列同源性比较显示,该序列编码了一种新的人类urocortin,其命名为urocortin III(UcnIII)。 虽然urocortin III对CRF-R1或CRF-R2没有高亲和力,但CRF-R2的亲和力大于对CRF-R1的亲和力。 Urocortin III能够刺激表达CRF-R2alpha或β的细胞中的环AMP产生。 因此,亲和力足够高,使得尿皮质素III可以作为CRF-R2的天然激动剂。 然而,urocortin III也可能是未被鉴定的受体的更强的激动剂。
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公开(公告)号:US06953838B2
公开(公告)日:2005-10-11
申请号:US10771224
申请日:2004-02-03
申请人: Wylie W. Vale, Jr. , Jean E. Rivier , Koichi S. Kunitake , Kathy A. Lewis , Marilyn H. Perrin , Jozsef Gulyas
发明人: Wylie W. Vale, Jr. , Jean E. Rivier , Koichi S. Kunitake , Kathy A. Lewis , Marilyn H. Perrin , Jozsef Gulyas
IPC分类号: C12N15/09 , A61K38/00 , A61K38/22 , A61P1/00 , A61P3/08 , A61P3/10 , A61P9/00 , A61P9/10 , A61P25/06 , A61P25/22 , A61P29/00 , A61P43/00 , C07H21/04 , C07K14/00 , C07K14/47 , C07K14/575 , C07K16/00 , C07K16/18 , C12P21/08 , C12Q1/02 , A61K39/00
CPC分类号: A61K38/2228 , A61K38/00 , C07K14/57509 , C07K14/695
摘要: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2α or β. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.
摘要翻译: 公众人类基因组数据库的搜索确定了人类EST,GenBank登录号AW293249,其与已知的河豚urocortin序列具有高同源性。 从人类基因组DNA扩增全长序列并进行测序。 新序列与人尿皮质素I和尿皮质素II的序列同源性比较显示,该序列编码了一种新的人类urocortin,其命名为urocortin III(UcnIII)。 虽然urocortin III对CRF-R1或CRF-R2没有高亲和力,但CRF-R2的亲和力大于对CRF-R1的亲和力。 Urocortin III能够刺激表达CRF-R2alpha或β的细胞中的环AMP产生。 因此,亲和力足够高,使得尿皮质素III可以作为CRF-R2的天然激动剂。 然而,urocortin III也可能是未被鉴定的受体的更强的激动剂。
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公开(公告)号:US06812210B2
公开(公告)日:2004-11-02
申请号:US10099766
申请日:2002-03-15
申请人: Wylie W. Vale, Jr. , Jean E. River , Koichi S. Kunitake , Kathy A. Lewis , Marilyn H. Perrin , Jozsef Gulyas
发明人: Wylie W. Vale, Jr. , Jean E. River , Koichi S. Kunitake , Kathy A. Lewis , Marilyn H. Perrin , Jozsef Gulyas
IPC分类号: A61K3800
CPC分类号: A61K38/2228 , A61K38/00 , C07K14/57509 , C07K14/695
摘要: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2&agr; or &bgr;. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.
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公开(公告)号:US6162896A
公开(公告)日:2000-12-19
申请号:US476123
申请日:1995-06-07
CPC分类号: C07K14/71 , A61K38/00 , C07K2319/00
摘要: In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein:an extracellular, ligand-binding domain,a hydrophobic, trans-membrane domain, andan intracellular, receptor domain having serine kinase-like activity.The invention receptors optionally further comprise a second hydrophobic domain at the amino terminus thereof. The invention receptor proteins are further characterized by having sufficient binding affinity for at least one member of the activin/TGF-.beta. superfamily of polypeptide growth factors such that concentrations of .ltoreq.10 nM of said polypeptide growth factor occupy .gtoreq.50% of the binding sites of said receptor protein. A presently preferred member of the invention superfamily of receptors binds specifically to activins, in preference to inhibins, transforming growth factory-.beta., and other non-activin-like proteins. DNA sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed.
摘要翻译: 根据本发明,提供了新的受体蛋白,其特征在于具有以下结构域,从所述蛋白质的N-末端读取:细胞外,配体结合结构域,疏水性,跨膜结构域和细胞内 ,具有丝氨酸激酶样活性的受体结构域。 本发明受体任选地还包含在其氨基末端的第二疏水结构域。 本发明受体蛋白的进一步特征在于对多肽生长因子的激活素/ TGF-β超家族的至少一个成员具有足够的结合亲和力,使得所述多肽生长因子的10nM的浓度占所述多肽生长因子的10% 所述受体蛋白的结合位点。 本发明目前优选的受体超家族成员特异性结合激活素,优于抑制素,转化生长工厂-β和其他非激活素样蛋白。 还公开了编码这种受体的DNA序列,使用其的测定法,以及由其衍生的抗体。
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公开(公告)号:US5910428A
公开(公告)日:1999-06-08
申请号:US637761
申请日:1996-07-02
IPC分类号: G01N33/53 , C07K7/08 , C07K14/72 , C12N5/10 , C12N15/09 , C12N15/12 , C12P21/02 , C12R1/91 , G01N33/566 , C07H21/04
CPC分类号: C07K14/72
摘要: Isolated, substantially pure mammalian brain-derived membrane-associated CRF-binding proteins and biologically active fragments thereof are provided as well as isolated and purified DNA fragments which encode the CRF binding proteins or biologically active fragments thereof or homologs of other mammalian species. By administering an amount of such CRF binding protein or a fragment thereof effective to modulate receptor activation, it is possible to modulate the action of CRF upon (a) the brain and nervous system, (b) the pituitary particularly for production of ACTH, beta endorphin and cortisol, (c) sites of inflammation, (d) the placenta, (e) the adrenal glands, (f) the gonads or (g) the gastrointestinal tract. Administration of an N-terminal fragment of the protein increases the binding site density for CRF and thus modulates its biological effect in vivo.
摘要翻译: PCT No.PCT / US94 / 12672 Sec。 371日期:1996年7月2日 102(e)日期1996年7月2日PCT 1994年11月7日PCT PCT。 公开号WO95 / 13372 日期1995年5月18日提供了分离的,基本上纯的哺乳动物脑衍生的膜相关CRF结合蛋白及其生物活性片段,以及分离和纯化的DNA片段,其编码CRF结合蛋白或其生物活性片段或其他哺乳动物的同源物 种类。 通过施用一定量的有效调节受体激活的CRF结合蛋白或其片段,有可能在(a)脑和神经系统调节CRF的作用,(b)垂体特别是用于产生ACTH,β 内啡肽和皮质醇,(c)炎症部位,(d)胎盘,(e)肾上腺,(f)性腺或(g)胃肠道。 施用蛋白质的N-末端片段增加CRF的结合位点密度,从而调节其在体内的生物学效应。
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公开(公告)号:US5464757A
公开(公告)日:1995-11-07
申请号:US97828
申请日:1993-07-23
申请人: Ellen Potter , Dominic P. Behan , Wolfgang H. Fischer , Elizabeth A. Linton , Philip J. Lowry , Wylie W. Vale, Jr.
发明人: Ellen Potter , Dominic P. Behan , Wolfgang H. Fischer , Elizabeth A. Linton , Philip J. Lowry , Wylie W. Vale, Jr.
IPC分类号: A61K38/00 , C07K14/47 , C07K16/18 , C12N15/12 , C12P21/08 , G01N33/566 , G01N33/68 , G01N33/74 , C07K14/435 , C12N15/16 , C12N15/63
CPC分类号: G01N33/566 , C07K14/47 , C07K16/18 , G01N33/6872 , G01N33/689 , G01N33/74 , A61K38/00 , G01N2800/368
摘要: A Corticotropin Releasing Factor-binding protein (CRF-BP) is isolated and purified sufficient to provide AA sequence data from which the DNA is obtained, which is then used to produce the protein recombinantly. The CRF-BP is useful for modulating the biological activity of CRF, such as reducing the high ACTH levels in mammals caused by excess CRF. The CRF-BP or fragments thereof and/or antibodies to the proteins may be employed in diagnostic assays to determine the levels of CRF, CRF-BP and the ratio of CRF/CRF-BP in a vascular fluid sample. The DNA or subsequence thereof can be used as probes for genetic material in certain assays. The anti-CRF-BP antibodies are also useful to purify the CRF-BP protein and to modulate the biological effect of CRF-BPs proteins.
摘要翻译: 分离和纯化促肾上腺皮质激素释放因子结合蛋白(CRF-BP),以提供获得DNA的AA序列数据,然后将其用于重组产生蛋白质。 CRF-BP可用于调节CRF的生物活性,例如降低由过量CRF引起的哺乳动物中的高ACTH水平。 CRF-BP或其片段和/或抗体可用于诊断测定中以确定血管流体样品中CRF,CRF-BP的水平和CRF / CRF-BP的比例。 在某些测定中,DNA或其子序列可用作遗传物质的探针。 抗CRF-BP抗体也可用于纯化CRF-BP蛋白并调节CRF-BPs蛋白的生物学作用。
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