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    • 2. 发明授权
    • Bovine GRF
    • 牛GRF
    • US4585756A
    • 1986-04-29
    • US541167
    • 1983-10-12
    • Paul E. Brazeau, Jr.Peter BohlenFrederick S. EschNicholas C. LingRoger C. L. Guillemin
    • Paul E. Brazeau, Jr.Peter BohlenFrederick S. EschNicholas C. LingRoger C. L. Guillemin
    • A61K38/00C07K14/60A61K37/02
    • C07K14/60A61K38/00Y10S930/12
    • 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.
    • 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。
    • 8. 发明授权
    • DNA encoding follistatin
    • 编码卵泡抑素的DNA
    • US5182375A
    • 1993-01-26
    • US708753
    • 1991-05-31
    • Nicholas C. K. LingNaoto UenoShunichi ShimasakiFrederick S. EschShao-Yao YingRoger C. L. Guillemin
    • Nicholas C. K. LingNaoto UenoShunichi ShimasakiFrederick S. EschShao-Yao YingRoger C. L. Guillemin
    • C07K14/47C07K14/575C12N15/12
    • C07K14/4703C07K14/575
    • 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.
    • 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。
    • 10. 发明授权
    • Inhibin and method of purifying same
    • 抑制剂及其纯化方法
    • US4740587A
    • 1988-04-26
    • US784436
    • 1985-10-03
    • Nicholas C. LingShao-Yao YingFred S. EschRoger C. L. Guillemin
    • Nicholas C. LingShao-Yao YingFred S. EschRoger C. L. Guillemin
    • C07K1/20A61K38/00C07K1/22C07K14/00C07K14/575A61K37/02C12P21/02
    • C07K14/575A61K38/00Y10S930/26
    • 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.
    • 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。