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    GRF analogs V
    2.
    发明授权
    GRF analogs V 失效
    GRF类似物V

    公开(公告)号：US4843064A

    公开(公告)日：1989-06-27

    申请号：US96513

    申请日：1987-09-11

    申请人： Joan Vaughan ,  Joachim Spiess ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    发明人： Joan Vaughan ,  Joachim Spiess ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    IPC分类号： A61K38/00 ,  C07K14/60

    CPC分类号： C07K14/60 ,  A61K38/00 ,  Y10S930/12

    摘要： The invention provides peptides which are particularly potent in stimulating the release of pituitary GH in fish and amphibians and which have a substantial portion or all of the following sequence: His-Ala-Asp-Gly-R.sub.5 -Phe-Asn-Lys-Ala-Tyr-Arg-Lys-Ala-Leu-Gly-Gln-Leu- Ser-Ala-Arg-Lys-Tyr-Leu-His-Thr-Leu-R.sub.27 -R.sub.28 -R.sub.29 -R.sub.30 -R.sub.31 -Gly-R.sub.33 -R.sub.34 -R.sub.35 -R.sub.36 -R.sub.37 - R.sub.38 -R.sub.39 -R.sub.40 -R.sub.41 -R.sub.42 -R.sub.43 -R.sub.44 -Ser wherein R.sub.5 is Met, Leu, Val, Nva, Gln, Thr, Ile or Nle; R.sub.27 is Met, Leu, Val, Nva, Gln, Thr, Ile or Nle; R.sub.28 is Ala, Ser or Asn; R.sub.29 is Lys or Arg; R.sub.30 is Arg or Gln; R.sub.31 is Val or Gln; R.sub.33 is Gly or Glu; R.sub.34 is Gly, Arg or Ser; R.sub.35 is Ser or Asn; R.sub.36 is Met, Leu, Val, Nva, Gln, Thr, Ile or Nle; R.sub.37 is Ile or Glu; R.sub.38 is Glu, Gln or Arg; R.sub.39 is Asp, Arg or Gly; R.sub.40 is Asp, Ser or Ala; R.sub.41 is Asn, Arg or Lys; R.sub.42 is Glu, Phe, Ala or Val; R.sub.43 is Pro, Asn or Arg; R.sub.44 is Leu or Ala. A sequence beginning at the C-terminus and extending part way or all the way to residue R.sub.27 may be deleted; a 29-residue peptide beginning at the N-terminus may be preferred. These peptides, as well as their nontoxic salts, are considered to be particularly useful in agriculture.

    摘要翻译： 本发明提供了在刺激鱼类和两栖动物中垂体GH释放特别有效的肽，其具有大部分或全部以下序列：His-Ala-Asp-Gly-R5-Phe-Asn-Lys-Ala- Tyr-Arg-Lys-Ala-Leu-Gly-Gln-Leu- Ser-Ala-Arg-Lys-Tyr-Leu-His-Thr-Leu-R27-R28-R29-R30-R31-Gly-R33-R34- R3为R5，R36-R37-R38-R39-R40-R41-R42-R43-R44-Ser，其中R5为Met，Leu，Val，Nva，Gln，Thr，Ile或Nle; R27是Met，Leu，Val，Nva，Gln，Thr，Ile或Nle; R28是Ala，Ser或Asn; R29为Lys或Arg; R30是Arg或Gln; R31为Val或Gln; R33是Gly或Glu; R34是Gly，Arg或Ser; R35是Ser或Asn; R36是Met，Leu，Val，Nva，Gln，Thr，Ile或Nle; R37是Ile或Glu; R38是Glu，Gln或Arg; R39为Asp，Arg或Gly; R40是Asp，Ser或Ala; R41是Asn，Arg或Lys; R42是Glu，Phe，Ala或Val; R43是Pro，Asn或Arg; R44是Leu或Ala，从C-末端开始并延伸到残基R27的一部分或全部的序列可以被删除; 可以优选从N末端开始的29残基肽。 这些肽以及它们的无毒盐被认为在农业中特别有用。

    Melanin-concentrating hormones
    3.
    发明授权
    Melanin-concentrating hormones 失效
    黑色素浓缩激素

    公开(公告)号：US5049655A

    公开(公告)日：1991-09-17

    申请号：US326984

    申请日：1989-03-22

    申请人： Joan Vaughan ,  Wolfgang H. Fischer ,  Jean E. F. Rivier ,  Jean-Louis M. Nahon ,  Francoise G. Presse ,  Wylie W. Vale, Jr.

    发明人： Joan Vaughan ,  Wolfgang H. Fischer ,  Jean E. F. Rivier ,  Jean-Louis M. Nahon ,  Francoise G. Presse ,  Wylie W. Vale, Jr.

    IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/04 ,  A61P35/00 ,  C07K7/06 ,  C07K7/08 ,  C07K7/64 ,  C07K14/00 ,  C07K14/575 ,  C12N15/12 ,  C12N15/16

    CPC分类号： C07K7/08 ,  C07K7/64 ,  A61K38/00 ,  Y10S530/827 ,  Y10S530/854

    摘要： Mammalian melanin-concentrating hormone (MCH) is isolated from rat tissue, purified and characterized. These MCH peptides are useful for treating skin disorders, for suppressing the proliferation of skin tumor cells, such as melanomas in mammals, and for modulating the secretion of ACTH. Generally, peptides are provided which have the following formula: ##STR1## or which are naturally occurring homologs of the peptide with said formula. The peptides which are the naturally occurring MCH homologs of mammalian species other than rat can also be obtained using the materials disclosed, as demonstrated specifically with human MCH, which is found to have the same structure as rat MCH. Also disclosed are the amino acid sequences of, and the nucleotide sequences of the cDNAs which encode, the putative precursors of rat MCH and human MCH. These precursors may also include one or more biologically active peptides N-terminally of the mature MCH's. Among these peptides, which are thought to be formed from the MCH precursors, are the peptide with the sequence H-Glu-Ile-Gly-Asp-Glu-Glu-Asn-Ser-Ala-Lys-Phe-Pro-Ile-NH.sub.2, which is cross-reactive with antibodies against alpha-MSH and CRF, and the peptide with the sequence H-Gly-X.sub.NGE -Phe-Pro-Ala-Glu-Asn-Gly-Val-Gln-Asn-Thr-Glu-Ser-Thr-Gln-Glu-OH, wherein X.sub.NGE is Pro-Ala-Val or Ser-Val-Ala, which is cross-reactive with antibodies against GRF.

    摘要翻译： 从大鼠组织中分离哺乳动物黑色素浓缩激素（MCH），进行纯化和表征。 这些MCH肽可用于治疗皮肤病症，抑制皮肤肿瘤细胞增殖，如哺乳动物的黑素瘤，以及调节ACTH的分泌。 通常，提供具有下式的肽：＆lt; IMAGE＆gt;或具有所述式的肽的天然存在同系物。 作为除大鼠之外的哺乳动物物种的天然存在的MCH同源物的肽也可以使用公开的材料获得，如用人MCH特异性证实的，其被发现具有与大鼠MCH相同的结构。 还公开了编码大鼠MCH和人MCH的推定前体的cDNA的氨基酸序列和cDNA的核苷酸序列。 这些前体还可以包括成熟MCH的N-末端的一种或多种生物活性肽。 在这些被认为由MCH前体形成的肽中，具有序列H-Glu-Ile-Gly-Asp-Glu-Glu-Asn-Ser-Ala-Lys-Phe-Pro-Ile-NH 2的肽 ，其与抗α-MSH和CRF的抗体具有交叉反应性，并且具有序列H-Gly-XNGE-Phe-Pro-Ala-Glu-Asn-Gly-Val-Gln-Asn-Thr-Glu-Ser -Thr-Gln-Glu -OH，其中XNGE是Pro-Ala-Val或Ser-Val-Ala，其与抗GRF的抗体交叉反应。

    Urocortin peptides, nucleic acid encoding same methods for using same
    4.
    发明授权
    Urocortin peptides, nucleic acid encoding same methods for using same 失效
    尿细胞肽，核酸编码方法相同

    公开(公告)号：US06214797B1

    公开(公告)日：2001-04-10

    申请号：US08981189

    申请日：1997-12-10

    申请人： Wylie W. Vale, Jr. ,  Joan Vaughan ,  Cynthia J. Donaldson ,  Kathy A. Lewis ,  Paul Sawchenko ,  Jean E. F. Rivier ,  Marilyn H. Perrin

    发明人： Wylie W. Vale, Jr. ,  Joan Vaughan ,  Cynthia J. Donaldson ,  Kathy A. Lewis ,  Paul Sawchenko ,  Jean E. F. Rivier ,  Marilyn H. Perrin

    IPC分类号： A61K3817

    CPC分类号： C07K14/57509 ,  A61K38/00

    摘要： Urocortin (Ucn) is a native mammalian peptide generally related to Urotensin I and Corticotropin Releasing Factor (CRF). Human Ucn has the formula: Asp-Asn-Pro-Ser-Leu-Ser-Ile-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Thr-Leu-Leu-Glu-Leu-Ala-Arg-Thr-Gln-Ser-Gln-Arg-Glu-Arg-Ala-Glu-Gln-Asn-Arg-Ile-Ile-Phe-Asp-Ser-Val-NH2 (SEQ ID NO:15). Rat-derived Ucn is identical but for 2 substitutions, Asp2 for Asn2 and Pro4 for Ser4. Ucn or analogs thereof or pharmaceutically acceptable salts can be administered to humans and other mammals to achieve substantial elevation of ACTH, &bgr;-endorphin, &bgr;-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone. They can also be used to lower blood pressure over an extended period of time, as stimulants to elevate mood and to improve memory and learning performance, as well as diagnostically. Shortened fragments may be administered to release endogenous CRF and/or Ucn in the brain and peripherally. Ucn antagonists can be used to block the action of Ucn and/or CRF, as can antibodies to Ucn. Labelled Ucn agonists and antagonists can be used in drug screening assays along with CRF receptors; they may also be used diagnostically along with Ucn antibodies.

    摘要翻译： Urocortin（Ucn）是通常与促进素I和促皮质素释放因子（CRF）相关的天然哺乳动物肽。 人Ucn具有下式：Asp-Asn-Pro-Ser-Leu-Ser-Ile-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Thr-Leu-Leu-Glu-Leu-Ala-Arg- Thr-Gln-Ser-Gln-Arg-Glu-Arg-Ala-Glu-Gln-Asn-Arg-Ile-Ile-Phe-Asp-Ser-Val-NH2（SEQ ID NO：15）。 大鼠衍生的Ucn是相同的，但是对于2个取代，As 2的Asp 2和Ser 4的Pro 4。 可以将Ucn或其类似物或药学上可接受的盐施用于人和其它哺乳动物，以实现ACTH，β-内啡肽，β-促脂解素，前 - 肌内注射皮质酮基因和皮质酮的其它产物的显着升高。 它们也可用于在较长时间内降低血压，作为兴奋剂提高心情，提高记忆力和学习表现以及诊断。 可以施用缩短的片段以释放脑中和外周的内源性CRF和/或Ucn。 Ucn拮抗剂可用于阻断Ucn和/或CRF的作用，以及Ucn的抗体。 标记的Uc激动剂和拮抗剂可与CRF受体一起用于药物筛选测定; 它们也可以与Ucn抗体一起在诊断上使用。

    DNA encoding NEI and NGE peptides
    5.
    发明授权
    DNA encoding NEI and NGE peptides 失效
    编码NEI和NGE肽的DNA

    公开(公告)号：US5449766A

    公开(公告)日：1995-09-12

    申请号：US208531

    申请日：1994-03-09

    申请人： Joan Vaughan ,  Wolfgang H. Fischer ,  Jean E. F. Rivier ,  Jean-Louis M. Nahon ,  Francoise G. Presse ,  Wylie W. Vale, Jr.

    发明人： Joan Vaughan ,  Wolfgang H. Fischer ,  Jean E. F. Rivier ,  Jean-Louis M. Nahon ,  Francoise G. Presse ,  Wylie W. Vale, Jr.

    IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/04 ,  A61P35/00 ,  C07K7/06 ,  C07K7/08 ,  C07K7/64 ,  C07K14/00 ,  C07K14/575 ,  C12N15/12 ,  C12N15/16 ,  C07H12/00 ,  C07H21/00 ,  C07K1/00 ,  C12P21/06

    CPC分类号： C07K7/08 ,  C07K7/64 ,  A61K38/00 ,  Y10S530/827 ,  Y10S530/854

    摘要： Mammalian melanin-concentrating hormone (MCH) is isolated from rat tissue, purified and characterized. These MCH peptides are useful for treating skin disorders, for suppressing the proliferation of skin tumor cells, such as melanomas in mammals, and for modulating the secretion of ACTH. Generally, peptides are provided which have the following formula: ##STR1## or which are naturally occurring homologs of the peptide with said formula. The peptides which are the naturally occurring MCH homologs of mammalian species other than rat can also be obtained using the materials disclosed, as demonstrated specifically with human MCH, which is found to have the same structure as rat MCH. Also disclosed are the amino acid sequences of, and the nucleotide sequences of the cDNAs which encode, the putative precursors of rat MCH and human MCH. These precursors may also include one or more biologically active peptides N-terminally of the mature MCH's. Among these peptides, which are thought to be formed from the MCH precursors, are the peptide with the sequence H-Glu-Ile-Gly-Asp-Glu-Glu-Asn-Ser-Ala-Lys-Phe-Pro-Ile-NH.sub.2, which is cross-reactive with antibodies against alpha-MSH and CRF, and the peptide with the sequence H-Gly-X.sub.NGE -Phe-Pro-Ala-Glu-Asn-Gly-Val-Gln-Asn-Thr-Glu-Ser-Thr-Gln-Glu-OH, wherein X.sub.NGE is Pro-Ala-Val or Ser-Val-Ala, which is cross-reactive with antibodies against GRF.

    摘要翻译： 从大鼠组织中分离哺乳动物黑色素浓缩激素（MCH），进行纯化和表征。 这些MCH肽可用于治疗皮肤病症，抑制皮肤肿瘤细胞增殖，如哺乳动物的黑素瘤，以及调节ACTH的分泌。 通常，提供具有下式的肽：＆lt; IMAGE＆gt;或具有所述式的肽的天然存在同系物。 作为除大鼠之外的哺乳动物物种的天然存在的MCH同源物的肽也可以使用公开的材料获得，如用人MCH特异性证实的，其被发现具有与大鼠MCH相同的结构。 还公开了编码大鼠MCH和人MCH的推定前体的cDNA的氨基酸序列和cDNA的核苷酸序列。 这些前体还可以包括成熟MCH的N-末端的一种或多种生物活性肽。 在这些被认为由MCH前体形成的肽中，具有序列H-Glu-Ile-Gly-Asp-Glu-Glu-Asn-Ser-Ala-Lys-Phe-Pro-Ile-NH 2的肽 ，其与抗α-MSH和CRF的抗体具有交叉反应性，并且具有序列H-Gly-XNGE-Phe-Pro-Ala-Glu-Asn-Gly-Val-Gln-Asn-Thr-Glu-Ser -Thr-Gln-Glu-OH，其中XNGE是Pro-Ala-Val或Ser-Val-Ala，其与抗GRF的抗体交叉反应。

    Potentiation of erythropoiesis
    6.
    发明授权
    Potentiation of erythropoiesis 失效
    红细胞生成的增强

    公开(公告)号：US5032507A

    公开(公告)日：1991-07-16

    申请号：US120470

    申请日：1987-11-13

    申请人： John Yu ,  Alice L. Yu ,  Joan Vaughan ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    发明人： John Yu ,  Alice L. Yu ,  Joan Vaughan ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    IPC分类号： A61K38/00 ,  A61K38/04 ,  A61K38/22 ,  A61P7/00 ,  C07K14/435 ,  C07K14/575

    CPC分类号： A61K38/22 ,  Y10S435/81

    摘要： A method for modulating the rate of erythropoiesis in human hematopoietic progenitor cells. FRP is found to be an efficacious potentiator of, and inhibin a suppressor of, erythropoietin-induced differentiation. FRP and inhibin are shown to be functional antagonists of each other, and thus represent an effective means for modulating erythropoiesis in a number of disease states which are directly caused by or associated with an abnormal rate of erythropoiesis.

    摘要翻译： 调节人类造血祖细胞中红细胞生成速率的方法。 发现FRP是促红细胞生成素诱导分化的有效增效剂，抑制抑制素。 FRP和抑制素显示为彼此的功能性拮抗剂，因此代表了直接由异常红细胞生成速率引起或与之相关的许多疾病状态调节红细胞生成的有效手段。

    Urocortin proteins and uses thereof
    7.
    发明申请
    Urocortin proteins and uses thereof 有权
    尿皮质蛋白及其用途

    公开(公告)号：US20070191592A1

    公开(公告)日：2007-08-16

    申请号：US11784317

    申请日：2007-04-05

    申请人： Wylie Vale ,  Teresa Reyes ,  Paul Sawchenko ,  Jean Rivier ,  Kathy Lewis ,  John Hogenesch ,  Joan Vaughan ,  Marilyn Perrin

    发明人： Wylie Vale ,  Teresa Reyes ,  Paul Sawchenko ,  Jean Rivier ,  Kathy Lewis ,  John Hogenesch ,  Joan Vaughan ,  Marilyn Perrin

    IPC分类号： C07K14/705 ,  A61K38/17 ,  C07H21/04 ,  C12P21/06 ,  C12N1/21 ,  C12N5/06 ,  C07K16/28

    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。