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    Mammalian PGRF
    2.
    发明授权
    Mammalian PGRF 失效
    哺乳动物PGRF

    公开(公告)号：US4517181A

    公开(公告)日：1985-05-14

    申请号：US418248

    申请日：1982-09-15

    申请人： Nicholas C. Ling ,  Frederick S. Esch ,  Peter Bohlen ,  Paul E. Brazeau, Jr. ,  Roger C. L. Guillemin

    发明人： Nicholas C. Ling ,  Frederick S. Esch ,  Peter Bohlen ,  Paul E. Brazeau, Jr. ,  Roger C. L. Guillemin

    IPC分类号： C07K14/575 ,  A23K1/16 ,  A61K20060101 ,  A61K38/00 ,  A61K38/04 ,  A61P5/00 ,  C07C20060101 ,  C07K14/00 ,  C07K14/60 ,  C07K14/61 ,  A61K37/02 ,  C07C103/52

    CPC分类号： C07K14/60 ,  A23K20/147 ,  A61K38/00 ,  Y10S930/12

    摘要： PGRF has been synthesized. The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in mammals and which have the formula: ##STR1## wherein R is OH or NH.sub.2, R.sub.34 is Ser or Ala, R.sub.38 is Arg or Ser, R.sub.40 is Ala or Arg and R.sub.41 is Arg, Arg-Ala, Arg-Ala-Arg, Arg-Ala-Arg-Leu or des-R.sub.41. These peptides or biologically active fragments thereof, or analogs thereof having well-known substitutions and/or additions, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to mammals, including humans, and may be used diagnostically.

    摘要翻译： PGRF已经合成。 本发明提供在刺激哺乳动物垂体GH释放方面非常有效的合成肽，其具有下式：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-Gln-Gln-Gly-Glu-R34-Asn-Gln-Glu- R38-Gly-R40-R41-R其中R是OH或NH2，R34是Ser或Ala，R38是Arg或Ser，R40是Ala或Arg，R41是Arg，Arg-Ala，Arg-Ala-Arg，Arg- Ala-Arg-Leu或des-R41。 具有众所周知的取代和/或添加的这些肽或其类似物或其类似物以及前述任何一种的无毒盐可以在治疗上施用于哺乳动物，包括人，并且可以在诊断上使用。

    Bovine GRF
    3.
    发明授权
    Bovine GRF 失效
    牛GRF

    公开(公告)号：US4585756A

    公开(公告)日：1986-04-29

    申请号：US541167

    申请日：1983-10-12

    申请人： Paul E. Brazeau, Jr. ,  Peter Bohlen ,  Frederick S. Esch ,  Nicholas C. Ling ,  Roger C. L. Guillemin

    发明人： Paul E. Brazeau, Jr. ,  Peter Bohlen ,  Frederick S. Esch ,  Nicholas C. Ling ,  Roger C. L. Guillemin

    IPC分类号： A61K38/00 ,  C07K14/60 ,  A61K37/02

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

    摘要： The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in mammals and which have the 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-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu-Gln-Gly-Ala-Lys-Val-Arg-Leu-Y wherein Y is OH or NH.sub.2. These peptides or biologically active fragments thereof, or analogs thereof having well-known substitutions and/or additions, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to mammals, including humans, and may be used diagnostically. The peptides are useful in stimulating the release of GH so as to accelerate growth in warm-blooded non-human animals, particularly cattle, and/or to increase the production of milk in lactating cows, and also in improving aquiculture.

    摘要翻译： 本发明提供了非常有效刺激哺乳动物垂体GH释放的合成肽，其具有下式：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-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu -Gln-Gly-Ala-Lys-Val-Arg-Leu-Y，其中Y是OH或NH2。 具有众所周知的取代和/或添加的这些肽或其类似物或其类似物以及前述任何一种的无毒盐可以在治疗上施用于哺乳动物，包括人，并且可以在诊断上使用。 这些肽可用于刺激GH的释放，以加速温血非人类动物，特别是牛的生长，和/或增加哺乳期牛的奶的产量，以及改善水产养殖。

    Porcine GRF
    4.
    发明授权
    Porcine GRF 失效
    猪GRF

    公开(公告)号：US4610976A

    公开(公告)日：1986-09-09

    申请号：US527292

    申请日：1983-08-29

    申请人： Peter Bohlen ,  Frederick S. Esch ,  Nicholas C. Ling ,  Paul E. Brazeau, Jr. ,  Roger C. L. Guillemin

    发明人： Peter Bohlen ,  Frederick S. Esch ,  Nicholas C. Ling ,  Paul E. Brazeau, Jr. ,  Roger C. L. Guillemin

    IPC分类号： A61K38/00 ,  C07K14/60 ,  C07K7/10 ,  A61K37/24

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

    摘要： The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in mammals and which have the 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-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu-Gln-Gly-Ala-Arg-Val-Arg-Leu-Y wherein Y is OH or NH.sub.2. These peptides or biologically active fragments thereof, or analogs thereof having well-known substitutions and, or additions, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to mammals, including humans, and may be used diagnostically. The peptides are useful in stimulating the release of GH and accelerating growth in warm-blooded non-human animals, particularly pigs, and in improving aquiculture.

    摘要翻译： 本发明提供了非常有效刺激哺乳动物垂体GH释放的合成肽，其具有下式：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-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu -Gln-Gly-Ala-Arg-Val-Arg-Leu-Y，其中Y是OH或NH2。 这些具有众所周知的替代和/或添加的肽或其类似物或其类似物以及前述任何一种的无毒盐可以在治疗上施用于包括人在内的哺乳动物，并且可以在诊断上使用。 这些肽可用于刺激GH的释放并加速温血非人类动物，特别是猪的生长和改善水产养殖。

    Glycosylated analogs of somatostatin
    5.
    发明授权
    Glycosylated analogs of somatostatin 失效
    生长抑素的糖基化类似物

    公开(公告)号：US4280953A

    公开(公告)日：1981-07-28

    申请号：US92647

    申请日：1979-11-08

    申请人： Roger C. L. Guillemin ,  Solange Lavielle ,  Paul E. Brazeau, Jr. ,  Nicholas C. Ling ,  Robert A. Benoit

    发明人： Roger C. L. Guillemin ,  Solange Lavielle ,  Paul E. Brazeau, Jr. ,  Nicholas C. Ling ,  Robert A. Benoit

    IPC分类号： A61K38/00 ,  C07K14/655 ,  C07C103/52 ,  A61K37/00

    CPC分类号： C07K14/655 ,  A61K38/00 ,  Y10S514/806 ,  Y10S930/16

    摘要： Somatostatin (SS) is modified to incorporate a carbohydrate moiety in the peptide chain by linkage to either Asn, Ser or Thr. The modified SS peptide analog may have the formula: ##STR1## wherein R.sub.1 is preferably a hexose or amino-hexose, such as glucose or N-acetylglucosamine. Alternatively, the carbohydrate can be linked to Ser or Thr by an ether bond. Such glycosomatostatins have an extended biological half-life compared to the parent peptide and substantially the same potency. Modifications and substitutions with respect to other amino acid residues in the chain can be made in the glycopeptides, for the purpose of increasing the effectiveness of SS analogs in other ways, and such increased effectiveness is a characteristic of the glycosomatostatin along with its longer-acting biological effect.

    摘要翻译： 修饰生长抑素（SS）以通过与Asn，Ser或Thr连接而在肽链中引入碳水化合物部分。 修饰的SS肽类似物可以具有下式：其中R 1优选为己糖或氨基己糖，例如葡萄糖或N-乙酰葡糖胺。 或者，碳水化合物可以通过醚键连接到Ser或Thr。 与母体肽相比，这种糖调节蛋白酶具有延长的生物半衰期和基本上相同的效力。 链中其他氨基酸残基的修饰和取代可以在糖肽中进行，目的是以其他方式提高SS类似物的有效性，而这种增加的有效性是糖基化抑制素与其长效 生物效应。

    Inhibin and method of purifying same
    6.
    发明授权
    Inhibin and method of purifying same 失效
    抑制剂及其纯化方法

    公开(公告)号：US4740587A

    公开(公告)日：1988-04-26

    申请号：US784436

    申请日：1985-10-03

    申请人： Nicholas C. Ling ,  Shao-Yao Ying ,  Fred S. Esch ,  Roger C. L. Guillemin

    发明人： Nicholas C. Ling ,  Shao-Yao Ying ,  Fred S. Esch ,  Roger C. L. Guillemin

    IPC分类号： C07K1/20 ,  A61K38/00 ,  C07K1/22 ,  C07K14/00 ,  C07K14/575 ,  A61K37/02 ,  C12P21/02

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

    摘要： Two 32,000-dalton proteins with inhibin activity were isolated from porcine follicular fluid using heparin-Sepharose affinity chromatography, followed by gel filtration on Sephacryl S-200 and then four steps of reverse-phase high-performance liquid chromatography. Each isolated molecular 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. Microsequencing revealed the NH.sub.2 -terminal portion of the 18K chain of both to be Ser-Thr-Ala-Pro-Leu-Pro-Trp-Pro-Trp-Ser-Pro-Ala-Ala-Leu-Arg-Leu-Leu-Gln-Arg-Pro-Pro-Glu-Glu-Pro-Ala-Val, of one of the 14K chains to be Gly-Leu-Glu-Cys-Asp-Gly-Arg-Thr-Asn-Leu-Cys-Cys-Arg-Gln-Gln-Phe-Phe-Ile-Asp-Phe-Arg-Leu-Ile-Gly-Trp, and of the other 14K chain to be Gly-Leu-Glu-Cys-Asp-Gly-Lys-Val-Asn-Ile-Cys-Cys-Lys-Lys-Gln-Phe-Phe-Val-Ser-Phe-Lys-Asp-Ile-Gly-Trp-Asn-Asp-Trp-Ile-Ile-Ala-Pro. Both proteins have now been completely characterized, each having a first chain 134 residues long linked by disulfide bonding to a second chain 116 or 115 residues long. The first chain is believed to be glycosylated, which accounts for the disparity between the number of residues and the apparent molecular weight of 18K. These 32K proteins specifically inhibit basal secretion of FSH, but not of LH, in a rat anterior pituitary monolayer culture system. The half-maximal effective does of one is 450 pg/ml and of the other is 900 pg/ml.

    摘要翻译： 使用肝素琼脂糖亲和层析从猪滤泡液中分离出两种具有抑制素活性的32,000道尔顿蛋白，然后在Sephacryl S-200上进行凝胶过滤，然后进行四步反相高效液相色谱。 每个分离的分子由分别为约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。 微测序显示18K链的NH 2末端部分为Ser-Thr-Ala-Pro-Leu-Pro-Trp-Pro-Trp-Ser-Pro-Ala-Ala-Leu-Arg-Leu-Leu-Gl Gly-Leu-Glu-Cys-Asp-Gly-Arg-Thr-Asn-Leu-Cys-Cys-Ala-14-N-Arg-Pro-Pro-Pro-Glu-Glu-Pro-Ala-Val Arg-Gln-Gln-Phe-Phe-Il-Asp-Phe-Arg-Leu-Ile-Gly-Trp，另外14K链为Gly-Leu-Glu-Cys-Asp-Gly-Lys-Val -Asn-Ile-Cys-Cys-Lys-Lys-Gln-Phe-Phe-Val-Ser-Phe-Lys-Asp-Ile-Gly-Trp-Asn-Asp-Trp-Ile-Ile-Ala-Pro。 两种蛋白质现在已被完全表征，每一种具有通过二硫键连接到第二链116或115个残基长的第一链134残基。 第一链被认为是糖基化的，这解释了残基数目和18K的表观分子量之间的差异。 这些32K蛋白特异性地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的基础分泌。 一半的最大有效值为450pg / ml，另一个为900pg / ml。

    Gonadostatin
    7.
    发明授权
    Gonadostatin 失效
    促性腺激素

    公开(公告)号：US4409139A

    公开(公告)日：1983-10-11

    申请号：US291294

    申请日：1981-08-10

    申请人： Nicholas C. Ling ,  Roger C. L. Guillemin ,  Shao-Yao Ying ,  Frederick S. Esch

    发明人： Nicholas C. Ling ,  Roger C. L. Guillemin ,  Shao-Yao Ying ,  Frederick S. Esch

    IPC分类号： A61K38/00 ,  C07K14/575 ,  C07G15/00

    CPC分类号： C07K14/575 ,  A61K38/00

    摘要： A substantially purified substance has been isolated from bovine gonadal secretions which mediates pituitary hormone secretion, using an extraction and purification sequence that includes gel filtration, partition chromatography and HPLC in that order. The substance, designated gonadostatin, is a moderate-size peptide which below a threshold level selectively inhibits LRF-stimulated pituitary secretion of LH and FSH. Above a threshold level, gonadostatin generally stimulates pituitary hormone secretion.

    摘要翻译： 已经从使用包括凝胶过滤，分配色谱和HPLC的提取和纯化序列的垂体激素分泌的牛性腺分泌物中分离出基本纯化的物质。 该物质指定的促性腺激素是一种低于阈值水平的中等大小的肽，选择性抑制LRF刺激的LH和FSH的垂体分泌。 高于阈值水平，促性腺激素通常会刺激垂体激素分泌。

    DNA encoding follistatin
    9.
    发明授权
    DNA encoding follistatin 失效
    编码卵泡抑素的DNA

    公开(公告)号：US5182375A

    公开(公告)日：1993-01-26

    申请号：US708753

    申请日：1991-05-31

    申请人： Nicholas C. K. Ling ,  Naoto Ueno ,  Shunichi Shimasaki ,  Frederick S. Esch ,  Shao-Yao Ying ,  Roger C. L. Guillemin

    发明人： Nicholas C. K. Ling ,  Naoto Ueno ,  Shunichi Shimasaki ,  Frederick S. Esch ,  Shao-Yao Ying ,  Roger C. L. Guillemin

    IPC分类号： C07K14/47 ,  C07K14/575 ,  C12N15/12

    CPC分类号： C07K14/4703 ,  C07K14/575

    摘要： Two follistatin proteins with inhibin-like activity were isolated from porcine follicular fluid using heparin-Sepharose affinity chromatography, followed by gel filtration on Sephacryl S-200 and then six steps of high-performance liquid chromatography. The larger protein has 315 residues and is believed to be glycosylated. The smaller protein is a 288-residue, C-terminally shortened version thereof. These proteins specifically inhibit basal secretion of FSH, but not of LH, in a rat anterior pituitary monolayer culture system. The half-maximal effective dose for both is 2.5-6.0 ng/ml. Human and rat follistatins exhibit very high homology with the porcine protein, with the human differing from porcine in only 4 residues out of 315 and with the rat differing from porcine in only 8 residues out of 315. Using the porcine amino acid sequence information, cDNA clones encoding these proteins were identified from a porcine ovarian cDNA library. Then, using the porcine cDNA as a probe, the cloning and sequencing of the corresponding human and rat proteins were accomplished.

    摘要翻译： 使用肝素琼脂糖亲和层析从猪滤泡液中分离两种具有抑制素样活性的卵泡抑素蛋白，然后在Sephacryl S-200上进行凝胶过滤，然后6步高效液相色谱。 较大的蛋白质具有315个残基并被认为是糖基化的。 较小的蛋白质是288残基，C末端缩短版本。 这些蛋白质特异性抑制大鼠垂体垂体单层培养系统中FSH的基础分泌，而不是LH的基础分泌。 两者的最大有效剂量为2.5-6.0ng / ml。 人和大鼠卵泡抑素与猪蛋白质具有非常高的同源性，人类与猪不同，仅315个中的4个残基中的猪，而315中仅有8个残基中的大鼠与猪不同。使用猪氨基酸序列信息，cDNA 从猪卵巢cDNA文库鉴定编码这些蛋白质的克隆。 然后，使用猪cDNA作为探针，完成相应的人和大鼠蛋白的克隆和测序。

    Mammalian follistatin
    10.
    发明授权
    Mammalian follistatin 失效
    哺乳动物卵泡抑素

    公开(公告)号：US5041538A

    公开(公告)日：1991-08-20

    申请号：US224432

    申请日：1988-07-26

    申请人： Nicholas C. K. Ling ,  Naoto Ueno ,  Shunichi Shimasaki ,  Frederick S. Esch ,  Shao-Yao Ying ,  Roger C. L. Guillemin

    发明人： Nicholas C. K. Ling ,  Naoto Ueno ,  Shunichi Shimasaki ,  Frederick S. Esch ,  Shao-Yao Ying ,  Roger C. L. Guillemin

    IPC分类号： C12N15/09 ,  A61K38/04 ,  C07K1/16 ,  C07K1/20 ,  C07K1/22 ,  C07K14/00 ,  C07K14/435 ,  C07K14/47 ,  C07K14/575 ,  C12N1/19 ,  C12N1/21 ,  C12P21/02 ,  C12R1/19 ,  C12R1/865

    CPC分类号： C07K14/4703 ,  C07K14/575

    摘要： Two follistatin proteins with inhibin-like activity were isolated from porcine follicular fluid using heparin-Sepharose affinity chromatography, followed by gel filtration on Sephacryl S-200 and then six steps of high-performance liquid chromatography. Each isolated molecule is a monomer having a molecular weight of at least about 32,000 daltons. Microsequencing revealed the NH.sub.2 -terminal portions both to be Gly-Asn-Cys-Trp-Leu-Arg-Gln-Ala-Lys-Asn-Gly-Arg-Cys-Gln-Val-Leu. The larger protein has 315 residues and is believed to be glycosylated. The smaller protein is a 288-residue, C-terminally shortened version thereof. These proteins specifically inhibit basal secretion of FSH, but not of LH, in a rat anterior pituitary monolayer culture system. The Half-maximal effective dose for both is 2.5-6.0 ng/ml. Human and rat follistatins exhibit very high homology with the porcine protein, with the human differing from porcine in only 4 residues out of 315 and with the rat differing from porcine in only 8 residues out of 315.

    摘要翻译： 使用肝素琼脂糖亲和层析从猪滤泡液中分离两种具有抑制素样活性的卵泡抑素蛋白，然后在Sephacryl S-200上进行凝胶过滤，然后6步高效液相色谱。 每个分离的分子是分子量至少约32,000道尔顿的单体。 微测序显示NH2-端部分均为Gly-Asn-Cys-Trp-Leu-Arg-Gln-Ala-Lys-Asn-Gly-Arg-Cys-Gln-Val-Leu。 较大的蛋白质具有315个残基并被认为是糖基化的。 较小的蛋白质是288残基，C末端缩短版本。 这些蛋白质特异性抑制大鼠垂体垂体单层培养系统中FSH的基础分泌，而不是LH的基础分泌。 两者的最大有效剂量为2.5-6.0ng / ml。 人和大鼠卵泡胰蛋白酶与猪蛋白质具有非常高的同源性，人类与猪不同，只有315个中只有4个残基，大鼠与猪不同，只有315个中只有8个残基。