-
公开(公告)号:US08044025B2
公开(公告)日:2011-10-25
申请号:US12632715
申请日:2009-12-07
申请人: Wylie W. Vale, Jr. , Teresa M. Reyes , Paul E. Sawchenko , Jean E. Rivier , Kathy A. Lewis , John B. Hogenesch , Joan M. Vaughan , Marilyn H. Perrin
发明人: Wylie W. Vale, Jr. , Teresa M. Reyes , Paul E. Sawchenko , Jean E. Rivier , Kathy A. Lewis , John B. Hogenesch , Joan M. Vaughan , Marilyn H. Perrin
CPC分类号: C07K14/57509 , A61K38/00 , A61K39/00
摘要: A human urocortin-related peptide with significant sequence homology to the CRF neuropeptide family was identified. A mouse cDNA was isolated from whole brain poly (A+) RNA that encodes a predicted 38 amino acid peptide protein designated herein as urocortin II. Both human URP and mouse Ucn II are structurally related to the other known mammalian family members, CRF and urocortin (Ucn). These peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn IL Synthesized Ucn-II and URP peptide binds with higher affinity to CRF-R2 than to CRF-R1 Ucn II and human URP appear to be involved in the regulation of body temperature and appetite and may play a role in other stress related phenomenon. These findings identify Ucn II and human URP as a new members of the CRF family of neuropeptides, which are expressed centrally and bind to CRF-R2.
摘要翻译: 鉴定出与CRF神经肽家族具有显着序列同源性的人尿皮质素相关肽。 从编码本文称为尿皮质素II的预测的38个氨基酸的肽蛋白质的全脑poly(A +)RNA中分离出小鼠cDNA。 人URP和小鼠Ucn II都与其他已知的哺乳动物家族成员CRF和尿皮质素(Ucn)结构相关。 这些肽在基底和应激条件下参与下丘脑 - 垂体 - 肾上腺轴的调节,这表明URP和Ucn IL的相似作用合成的Ucn-II和URP肽与CRF-R2的亲和力高于CRF-R1 Ucn II和人类URP似乎参与了体温和食欲的调节,可能在其他压力相关现象中起作用。 这些发现将Ucn II和人类URP鉴定为CRF家族的新成员,它们集中表达并结合CRF-R2。
-
公开(公告)号:US06838274B2
公开(公告)日:2005-01-04
申请号:US09919473
申请日:2001-07-31
申请人: Wylie W. Vale, Jr. , Teresa M. Reyes , Paul E. Sawchenko , Jean E. Rivier , Kathy A. Lewis , John B. Hogenesch , Joan M. Vaughan , Marilyn H. Perrin
发明人: Wylie W. Vale, Jr. , Teresa M. Reyes , Paul E. Sawchenko , Jean E. Rivier , Kathy A. Lewis , John B. Hogenesch , Joan M. Vaughan , Marilyn H. Perrin
IPC分类号: C12N15/09 , A61K38/00 , A61K38/22 , A61K39/00 , A61P3/00 , A61P5/06 , A61P9/04 , A61P9/10 , A61P25/18 , A61P25/22 , A61P25/24 , A61P25/26 , A61P25/28 , A61P29/00 , C07K14/435 , C07K14/52 , C07K14/575 , C07K16/24 , C12N1/21 , C12N5/10 , C12N15/12 , C12N15/16 , C12P21/08 , C12R1/19 , C12N15/63
CPC分类号: C07K14/57509 , A61K38/00 , A61K39/00
摘要: A human urocortin-related peptide with significant sequence homology to the CRF neuropeptide family was identified. A mouse cDNA was isolated from whole brain poly (A+) RNA that encodes a predicted 38 amino acid peptide protein designated herein as urocortin II. Both human URP and mouse Ucn II are structurally related to the other known mammalian family members, CRF and urocortin (Ucn). These peptides are involved in the regulation of the hypothalamic-pituituary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn II. Synthesized Ucn-II and URP peptide binds with higher affinity to CRF-R2 than to CRF-R1 Ucn II and human URP appear to be involved in the regulation of body temperature and appetite and may play a role in other stress related phenomenon. These findings identify Ucn II and human URP as a new members of the CRF family of neuropeptides, which are expressed centrally and bind to CRF-R2.
摘要翻译: 鉴定出与CRF神经肽家族具有显着序列同源性的人尿皮质素相关肽。 从编码本文称为尿皮质素II的预测的38个氨基酸的肽蛋白质的全脑poly(A +)RNA中分离出小鼠cDNA。 人URP和小鼠Ucn II都与其他已知的哺乳动物家族成员CRF和尿皮质素(Ucn)结构相关。 这些肽在基础和应激条件下参与下丘脑 - 垂体 - 肾上腺轴的调节,表明URP和Ucn II具有类似的作用。 合成的Ucn-II和URP肽以比CRF-R1 Ucn II更高的亲和力结合,并且人URP似乎参与体温和食欲的调节,并且可能在其他压力相关现象中起作用。 这些发现将Ucn II和人类URP鉴定为CRF家族的新成员,它们集中表达并结合CRF-R2。
-
公开(公告)号:US20100168021A1
公开(公告)日:2010-07-01
申请号:US12632715
申请日:2009-12-07
申请人: Wylie Walker Vale, JR. , Teresa M. Reyes , Paul E. Sawchenko , Jean E. Rivier , Kathy A. Lewis , John B. Hogenesch , Joan M. Vaughan , Marilyn H. Perrin
发明人: Wylie Walker Vale, JR. , Teresa M. Reyes , Paul E. Sawchenko , Jean E. Rivier , Kathy A. Lewis , John B. Hogenesch , Joan M. Vaughan , Marilyn H. Perrin
CPC分类号: C07K14/57509 , A61K38/00 , A61K39/00
摘要: A human urocortin-related peptide with significant sequence homology to the CRF neuropeptide family was identified. A mouse cDNA was isolated from whole brain poly (A+) RNA that encodes a predicted 38 amino acid peptide protein designated herein as urocortin II. Both human URP and mouse Ucn II are structurally related to the other known mammalian family members, CRF and urocortin (Ucn). These peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn IL Synthesized Ucn-II and URP peptide binds with higher affinity to CRF-R2 than to CRF-R1 Ucn II and human URP appear to be involved in the regulation of body temperature and appetite and may play a role in other stress related phenomenon. These findings identify Ucn II and human URP as a new members of the CRF family of neuropeptides, which are expressed centrally and bind to CRF-R2.
摘要翻译: 鉴定出与CRF神经肽家族具有显着序列同源性的人尿皮质素相关肽。 从编码本文称为尿皮质素II的预测的38个氨基酸的肽蛋白质的全脑poly(A +)RNA中分离出小鼠cDNA。 人URP和小鼠Ucn II都与其他已知的哺乳动物家族成员CRF和尿皮质素(Ucn)结构相关。 这些肽在基底和应激条件下参与下丘脑 - 垂体 - 肾上腺轴的调节,这表明URP和Ucn IL的相似作用合成的Ucn-II和URP肽与CRF-R2的亲和力高于CRF-R1 Ucn II和人类URP似乎参与了体温和食欲的调节,可能在其他压力相关现象中起作用。 这些发现将Ucn II和人类URP鉴定为CRF家族的新成员,它们集中表达并结合CRF-R2。
-
公开(公告)号:US20120270792A1
公开(公告)日:2012-10-25
申请号:US13328821
申请日:2011-12-16
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
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-R2α或bgr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。
-
公开(公告)号:US08084413B2
公开(公告)日:2011-12-27
申请号:US12266430
申请日:2008-11-06
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-R2α或bgr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。
-
公开(公告)号:US08445425B2
公开(公告)日:2013-05-21
申请号:US13328821
申请日:2011-12-16
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.
-
公开(公告)号:US20090156493A1
公开(公告)日:2009-06-18
申请号:US12266430
申请日:2008-11-06
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
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。
-
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。
-
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。
-
公开(公告)号:US07869958B2
公开(公告)日:2011-01-11
申请号:US11199821
申请日:2005-08-09
申请人: Grace Christy Rani Royappa , Marilyn H. Perrin , Jean E. Rivier , Wylie W. Vale, Jr. , Roland Riek
发明人: Grace Christy Rani Royappa , Marilyn H. Perrin , Jean E. Rivier , Wylie W. Vale, Jr. , Roland Riek
IPC分类号: G06G7/58
CPC分类号: C07K14/723 , C07K2299/00 , G01N2333/726 , G06F19/16 , G06F19/18
摘要: The present invention relates to a method for identifying modulators of B1 G-protein coupled receptors. The present invention also relates to a method for identifying an antagonist or agonist of the corticotropin-releasing factor receptor 2 (CRFR2). The present invention also relates to a method for improving antagonists or agonists of CRFR2. The present invention also relates to the three-dimensional structure of CRFR2 as representative of the B1 GPCR subfamily and its use as a basis for rational drug design of antagonist or agonists of B1 GPCRs.
摘要翻译: 本发明涉及用于鉴定B1G-蛋白偶联受体调节剂的方法。 本发明还涉及用于鉴定促肾上腺皮质激素释放因子受体2(CRFR2)的拮抗剂或激动剂的方法。 本发明还涉及一种改善CRFR2拮抗剂或激动剂的方法。 本发明还涉及作为B1GPCR亚族的代表性的CRFR2的三维结构及其作为B1GPCR的拮抗剂或激动剂的合理药物设计的基础的用途。
-
-
-
-
-
-
-
-
-