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公开(公告)号:US5155214A
公开(公告)日:1992-10-13
申请号:US462126
申请日:1990-01-08
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 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bFGF。
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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:US4605643A
公开(公告)日:1986-08-12
申请号:US585814
申请日:1984-03-02
CPC分类号: C07K14/60 , A61K38/00 , Y10S930/12
摘要: A synthetic peptide is extremely potent in stimulating the release of pituitary GH in mammals, particularly in sheep, since it is the replicate of the native (hormone) releasing factor of the sheep hypothalamus. It contains the following sequence: Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Ile-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. This peptide or a biologically active fragment 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 and may be used diagnostically. The peptide is particularly useful in stimulating the release of GH so as to accelerate growth in warm-blooded non-human animals, particularly sheep, and/or to improve aquiculture.
摘要翻译: 合成肽在刺激哺乳动物,特别是绵羊中垂体GH的释放方面是非常有效的,因为它是羊下丘脑的天然(激素)释放因子的复制物。 它含有以下序列:Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Ile-Leu-Gly-Gln-Leu-Se r-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。 具有众所周知的取代和/或添加的这种肽或其生物活性片段或其类似物以及前述任何一种的无毒盐可以在哺乳动物的治疗上施用,并且可以在诊断上使用。 该肽特别可用于刺激GH的释放,以加速温血非人类动物,特别是绵羊的生长和/或改善水产养殖。
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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: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。
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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。
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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: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: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: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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