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公开(公告)号：US4316891A
公开(公告)日：1982-02-23
申请号：US159801
申请日：1980-06-14
IPC分类号： A61K38/00 , C07K14/655 , A61K37/00 , C07C103/52
CPC分类号： C07K14/6555 , A61K38/00 , Y10S514/806 , Y10S930/16
摘要： 28-member residue and 25-member residue peptides have been synthesized containing the tetradecapeptide somatostatin that are more potent than somatostatin. Somatostatin-28 has the formula: ##STR1## The three N-terminal amino acid residues are absent in somatostatin-25. Somatostatin-28 or somatostatin-25 or a pharmaceutically acceptable addition salt thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals in the same manner as somatostatin.
摘要翻译： 已经合成了含有比生长抑素更有效的十四肽生长抑素的28个残基和25个残基的肽。 生长抑素-28具有下式：H-Ser-Ala-Asn-Ser-Asn-Pro-Ala-Met-Ala-Pro-Arg-Glu-Arg-Lys- + TR三个N末端氨基酸残基 在生长抑素-25中不存在。 分散在药学上可接受的液体或固体载体中的生长抑素-28或生长抑素-25或其药学上可接受的加成盐可以以与生长抑素相同的方式施用于哺乳动物。
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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
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。
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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。
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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
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。
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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。
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公开(公告)号：US4740587A
公开(公告)日：1988-04-26
申请号：US784436
申请日：1985-10-03
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。
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公开(公告)号：US4409139A
公开(公告)日：1983-10-11
申请号：US291294
申请日：1981-08-10
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。
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公开(公告)号：US4973577A
公开(公告)日：1990-11-27
申请号：US091696
申请日：1987-08-31
申请人： Wylie W. Vale, Jr. , Jean E. F. Rivier , Richard A. McClintock , Anne Corrigan , Joan Vaughan , Joachim Spiess , Nicholas C. Ling , Shao-Yao Ying , Frederick S. Esch , Roger C. L. Guillemin
发明人： Wylie W. Vale, Jr. , Jean E. F. Rivier , Richard A. McClintock , Anne Corrigan , Joan Vaughan , Joachim Spiess , Nicholas C. Ling , Shao-Yao Ying , Frederick S. Esch , Roger C. L. Guillemin
IPC分类号： A61K38/00 , C07K14/575
CPC分类号： C07K14/575 , A61K38/00 , Y10S514/80
摘要： A 28,000-dalton protein with FSH-releasing activity is isolated from porcine follicular fluid in a multi-step procedure including gel filtration, ion exchange chromatography and several reverse-phase high-performance liquid chromatography steps. The 28 kD protein promotes secretion of FSH, but not of LH, in a rat anterior pituitary monolayer culture system, exhibiting an EC.sub.50 of 0.5 ng/ml. These peptides are dimers of inhibin .beta.-chains of mammals, and homodimers or heterodimers of the .beta..sub.A and .beta..sub.B chains are biologically active to regulate fertility of various mammalian species, including humans.
摘要翻译： 具有FSH释放活性的28,000道尔顿蛋白质以多步法从猪滤泡液中分离，包括凝胶过滤，离子交换层析和几个反相高效液相色谱步骤。 在大鼠垂体前叶单层培养系统中，28kD蛋白促进FSH的分泌，但不促进LH的分泌，其表现为0.5ng / ml的EC 50。 这些肽是哺乳动物的抑制素β-链的二聚体，βA和βB链的同源二聚体或异源二聚体具有生物学活性，以调节各种哺乳动物物种（包括人类）的生育力。
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公开(公告)号：US5464774A
公开(公告)日：1995-11-07
申请号：US139953
申请日：1987-12-31
CPC分类号： C07K14/503 , A61K38/00
摘要： Substantially pure mammalian basic fibroblast growth factors are produced. The amino acid residue sequences of bovine and human bFGF are disclosed as well as a DNA chain encoding the polypeptide of the bovine species. By appropriately inserting a synthesized DNA chain into a cloning vector and using the cloning vector to transform cells, synthetic bovin bFGF can be obtained from transformed cell lines, both prokaryotic and eukaryotic.
摘要翻译： 产生基本纯化的哺乳动物碱性成纤维细胞生长因子。 公开了牛和人bFGF的氨基酸残基序列以及编码牛种多肽的DNA链。 通过将合成的DNA链适当地插入到克隆载体中并使用克隆载体来转化细胞，可以从原核和真核的转化细胞系获得合成的bovin bFGF。
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公开(公告)号：US4956455A
公开(公告)日：1990-09-11
申请号：US747154
申请日：1985-06-20
IPC分类号： C12N15/00 , A61K38/00 , C07K14/00 , C07K14/50 , C12N1/16 , C12N1/19 , C12N1/20 , C12N1/21 , C12N15/09 , C12N15/12 , C12P21/02 , C12R1/19 , C12R1/865 , C12R1/91
CPC分类号： C07K14/503 , A61K38/00 , Y10S530/82 , Y10S530/827 , Y10S530/839
摘要： Substantially pure bovine pituitary fibroblast growth factor, a 146 amino acid residue polypeptide, is produced. The amino acid residue sequence of bpFGF is disclosed as well as a DNA chain encoding the polypeptide. By appropriately inserting a synthesized DNA chain into a cloning vector and using the cloning vector to transform cells, synthetic bpFGF can be obtained from transformed cell lines, both prokaryotic and eukaryotic.
摘要翻译： 产生基本上纯的牛垂体成纤维细胞生长因子146个氨基酸残基多肽。 公开了bpFGF的氨基酸残基序列以及编码该多肽的DNA链。 通过将合成的DNA链适当地插入到克隆载体中并使用克隆载体来转化细胞，可以从原核和真核的转化细胞系获得合成的bpFGF。
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