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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。

    Human inhibin
    3.
    发明授权
    Human inhibin 失效
    人抑制素

    公开(公告)号：US4737578A

    公开(公告)日：1988-04-12

    申请号：US848924

    申请日：1986-04-07

    申请人： Ronald M. Evans ,  Michael G. Rosenfeld ,  Gail Cerelli ,  Kelly E. Mayo ,  Joachim Spiess ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    发明人： Ronald M. Evans ,  Michael G. Rosenfeld ,  Gail Cerelli ,  Kelly E. Mayo ,  Joachim Spiess ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    IPC分类号： A61K38/00 ,  C07K14/575 ,  C07K7/10 ,  C07K13/00

    CPC分类号： C07K14/575 ,  A61K38/00 ,  Y10S930/26

    摘要： Proteins with inhibin activity having a weight of about 32,000 daltons. The molecule is composed of two chains having molecular weights of about 18,000 and about 14,000 daltons, respectively, which are bound together by disulfide bonding. The 18K chain is obtained from the human inhibin gene and has the formula: H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu-Gln-Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Leu-Asn-Ile-Ser-Phe-Gln-Glu-Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R.sub.65 -Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His-Ile-Pro-Pro-Asn-Leu-Ser-Leu-Pro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly-Ala-Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pro-Leu-His-Val-Arg-Thr-Thr-Ser-Asp-Gly-Gly-Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH, wherein R.sub.65 is Ile or Arg. The 18K chain is connected by disulfide bonding to the 14K chain.

    摘要翻译： 具有约32,000道尔顿重量的具有抑制素活性的蛋白质。 该分子由分子量分别为约18,000和约14,000道尔顿的两条链组成，它们通过二硫键结合在一起。 18K链由人抑制素基因得到，具有下式：H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu Gln-Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Le-Asn-Ile-Ser-Phe-Gln-Glu- Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R65-Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His- Ile-Pro-Pro-As n-Leu-Ser-Leu-Pro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly -Ala-Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pr-Leu-His-Val-Arg-Thr-Thr-Ser-Asp-Gly-Gly- Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH，其中R65是Ile或Arg。 18K链通过二硫键与14K链连接。

    Melanin-concentrating hormones
    5.
    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。

    Ovine inhibin
    6.
    发明授权
    Ovine inhibin 失效
    牛抑制素

    公开(公告)号：US5015729A

    公开(公告)日：1991-05-14

    申请号：US210683

    申请日：1988-06-23

    申请人： Joachim Spiess ,  Jean E. F. Rivier ,  C. Wayne Bardin ,  Wylie W. Vale, Jr.

    发明人： Joachim Spiess ,  Jean E. F. Rivier ,  C. Wayne Bardin ,  Wylie W. Vale, Jr.

    IPC分类号： A61K38/00 ,  C07K14/575 ,  C07K16/26

    CPC分类号： C07K14/575 ,  C07K16/26 ,  A61K38/00

    摘要： A dimeric protein with inhibin activity is isolated from ram reta testis fluid using reverse-phase high-performance liquid chromatography and gel filtration. The isolated molecule is composed of two chains having apparent molecular weights of about 18,000 and about 16,500 to 14,500 Daltons, as measured by gel electrophoresis, which are bound together by disulfide bonding and the longer of which is likely glycosylated. Microsequencing revealed the NH.sub.2 -terminal portion of the longer chain to be Ser- Thr-Pro-Pro-Leu-Pro-Trp-Pro-Trp-Ser-Pro-Ala-Ala-Leu-Arg-Leu-Gln-Arg-Pro-Pro- Glu-Glu-Pro-Ala-Ala-His-Ala-Asp-Cys and of the shorther chain to by Gly-Leu-Glu-Cys-Asp-Gly-Lys-Val-Asn-Ile-Cys-Cys-Lys-Lys-Gln-Phe. This dimeric protein specifically inhibits basal secretion of FSH, but not of LH, in a rat anterior pituitary monolayer culture system, exhibiting a half-maximal effective dose of about 0.1 to 0.3 ng/ml. Furthermore, antibodies raised against synthetic replicates of the N-terminal six residues of the longer chain, as well as against the N-terminal 25 residues, are effective to reduce the activity of highly purified intact ovine inhibin and might be used to exert a profertility effect in rams, ewes and other mammals.

    摘要翻译： 使用反相高效液相色谱和凝胶过滤从ram reta睾丸液中分离具有抑制素活性的二聚体蛋白。 分离的分子由具有约18,000和约16,500至14,500道尔顿的两条链组成，通过凝胶电泳测量，其通过二硫键结合在一起，并且其中较长的可能被糖基化。 Microsequencing显示较长链的NH 2末端部分为Ser-Thr-Pro-Pro-Leu-Pro-Trp-Pro-Trp-Ser-Pro-Ala-Ala-Leu-Arg-Leu-Gln-Arg-Pr 通过Gly-Leu-Glu-Cys-Asp-Gly-Lys-Val-Asn-Ile-Cys-Ala-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asp-Cys， Cys-Lys-Lys-Gln-Phe。 这种二聚体蛋白特异性抑制大鼠垂体前叶垂体单层培养系统中FSH的基础分泌而不是LH分泌，表现出约0.1至0.3ng / ml的最大有效剂量。 此外，针对长链的N末端六个残基以及N末端25个残基的合成重复产生的抗体对于降低高度纯化的完整羊抑制素的活性是有效的，并且可以用于发挥促进作用 对公羊，母羊和其他哺乳动物的影响。

    Human pancreatic GRF amidated fragments
    7.
    发明授权
    Human pancreatic GRF amidated fragments 失效
    人胰腺GRF酰化片段

    公开(公告)号：US4703035A

    公开(公告)日：1987-10-27

    申请号：US782912

    申请日：1985-10-02

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

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

    IPC分类号： A61K38/00 ,  C07K14/60 ,  A61K37/36 ,  A61K37/43 ,  C07K7/10

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

    摘要： Surprisingly active fragments of human pancreatic GRF have been synthesized which exhibit good biological activity. These synthetic peptides are extremely potent in stimulating the release of pituitary GH in humans and in nonhuman animals and have the general formula: H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Y wherein Y is NH.sub.2, Gln-NH.sub.2, Gln-Gln-NH.sub.2 or Gln-Gln-Gly-NH.sub.2. Two such fragments have been tested, namely the 29 and the 32 N-terminal residue sequences that are amidated at the C-terminus. These peptides, as well as nontoxic salts thereof, may be administered therapeutically to animals, including humans.

    摘要翻译： 已经合成了人胰腺GRF的惊人活性片段，其表现出良好的生物学活性。 这些合成肽在刺激人和非人动物中垂体GH的释放方面非常有效，具有以下通式：H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys -Val-Leu-Gly-Gln-Leu- Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Y，其中Y是NH2，Gln-NH2，Gln-Gln-NH2 或Gln-Gln-Gly-NH 2。 已经测试了两个这样的片段，即在C末端酰胺化的29个和32个N-末端残基序列。 这些肽以及其无毒盐可以治疗性地给予动物，包括人。

    CRF And analogs
    8.
    发明授权
    CRF And analogs 失效
    CRF和类比

    公开(公告)号：US4415558A

    公开(公告)日：1983-11-15

    申请号：US378999

    申请日：1982-05-17

    申请人： Wylie W. Vale, Jr. ,  Joachim Spiess ,  Catherine L. Rivier ,  Jean E. F. Rivier

    发明人： Wylie W. Vale, Jr. ,  Joachim Spiess ,  Catherine L. Rivier ,  Jean E. F. Rivier

    IPC分类号： A61K38/00 ,  C07K14/575 ,  A61K37/00 ,  C07C103/52

    CPC分类号： C07K14/57509 ,  A61K38/00 ,  Y10S514/805

    摘要： CRF (Corticotropin Releasing Factor) has the formula:H-Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Thr-Lys-Ala-Asp-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Leu-Asp-Ile-Ala-NH.sub.2.Analogs have been synthesized that are at least as potent as CRF, and CRF or these analogs or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals to achieve a substantial elevation of ACTH, .beta.-endorphin, .beta.-lipotropin and corticosterone levels and/or a lowering of blood pressure over an extended period of time. In the analogs, one or more of the first three N-terminal residues may be deleted or may be substituted by a peptide up to 10 amino acids long and/or by an acylating agent containing up to 7 carbon atoms. Ala in the 41-position may also be substituted or deleted so long as the remaining C-terminus is amidated. Several other substitutions may also be made throughout the chain.

    摘要翻译： CRF（促皮质素释放因子）具有下式：H-Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu- Glu-Met-Thr-Lys-Ala-Asp-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Ar g-Lys-Leu-Leu-Asp-Ile-Ala-NH 2。 已经合成至少与CRF一样有效的类似物，并且分散在药学上可接受的液体或固体载体中的CRF或这些类似物或其药学上可接受的盐可以施用于哺乳动物以实现ACTH，β-内啡肽的显着升高 ，β-促凝血酶和皮质酮水平和/或在长时间内降低血压。 在类似物中，前三个N末端残基中的一个或多个可以被缺失或可被长达10个氨基酸的肽和/或被含有至多7个碳原子的酰化剂所取代。 41位的Ala也可以被取代或缺失，只要其余的C末端被酰胺化即可。 还可以在整个链中进行几个其它取代。

    Urocortin peptides, nucleic acid encoding same methods for using same
    9.
    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
    10.
    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。