公开(公告)号：US5681928A

公开(公告)日：1997-10-28

申请号：US358184

申请日：1994-12-16

申请人： Jean E. F. Rivier ,  John S. Porter

发明人： Jean E. F. Rivier ,  John S. Porter

IPC分类号： G01N33/48 ,  A61K38/00 ,  C07C233/47 ,  C07C233/56 ,  C07C235/42 ,  C07C271/22 ,  C07C279/14 ,  C07K1/04 ,  C07K1/10 ,  C07K7/06 ,  C07K7/23 ,  C07K14/575 ,  C07K14/655 ,  G01N33/68 ,  C07K1/00

CPC分类号： C07C271/22 ,  C07C233/47 ,  C07C233/56 ,  C07C235/42 ,  C07C279/14 ,  C07K1/047 ,  C07K14/57509 ,  C07K14/655 ,  C07K7/23 ,  A61K38/00

摘要： Compounds are provided termed "betides" which mimic peptides and which contain one or more residues of aminoglycine, C.sup..alpha. -aminoalanine, aminosarcosine or the like wherein the side chain amino group has been acylated and optionally also alkylated. Generally, betides have the formula: X.sub.N --X.sub.1 --X.sub.2 --X.sub.3 --X.sub.m --X.sub.4 --X.sub.5 --X.sub.6 --X.sub.C, where X.sub.N is an acyl or other N-terminal group or a peptide up to about 50 amino acids in length having such a group; X.sub.C is OH, NH.sub.2 or other C-terminal group or a peptide up to about 50 amino acids in length having such a group; and X.sub.1 -X.sub.6 are each independently a betide amino acid or .alpha.-amino acid or des-X; and X.sub.m is a peptide up to about 50 amino acids or des-X; provided however that at least one of X.sub.1 -X.sub.6 is a betide amino acid residue having the formula: ##STR1## wherein R.sub.o is H or CH.sub.3, R and R.sub.2 are H or lower alkyl, and R.sub.3 is an acyl group, an isocyanate group, an isothiocyanate group or a sulfonyl group. In methods for making betides, an aminoglycine residue can be subjected to side chain acylation, and optionally also alkylation, after it has been incorporated into a peptide intermediate. This method can be used as a valuable tool to synthesize and screen multiple substituents at one or more positions in a peptide, permitting simultaneous screening of betides which mimic peptides having a large number of natural or unnatural amino acid substituents at a particular position, and optionally both D- and L-isomers of those substituents.

摘要翻译： 化合物被提供为模拟肽并且含有一个或多个氨基糖，C 1 - 氨基丙氨酸，氨基肌氨酸等残基的其中侧链氨基已被酰化并任选也被烷基化的“内含子”。 一般来说，肽具有下式：XN-X1-X2-X3-Xm-X4-X5-X6-XC，其中XN是酰基或其它N-末端基团或长达约50个氨基酸的肽，具有这样的 组; XC是OH，NH2或其它C末端基或长达约50个氨基酸的肽，具有这样的基团; 和X 1 -X 6各自独立地为β-氨基酸或α-氨基酸或des-X; Xm是至多约50个氨基酸或des-X的肽; 但是X-X6中的至少一个是具有下式的下式氨基酸残基：其中Ro是H或CH3，R和R2是H或低级烷基，R3是酰基，异氰酸酯基， 异硫氰酸酯基或磺酰基。 在制备甜菜碱的方法中，氨基糖残基可以在其被并入肽中间体之后进行侧链酰化，并且任选地也可以烷基化。 该方法可用作合成和筛选肽中一个或多个位置上的多个取代基的有价值工具，允许同时筛选模拟在特定位置具有大量天然或非天然氨基酸取代基的肽的肽，以及任选地 那些取代基的D-和L-异构体都是这样的。

公开(公告)号：US5663292A

公开(公告)日：1997-09-02

申请号：US353928

申请日：1994-12-12

申请人： Jean E. F. Rivier

发明人： Jean E. F. Rivier

IPC分类号： G01N33/15 ,  A61K38/00 ,  A61K38/04 ,  A61K45/00 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  C07K14/575 ,  G01N33/50 ,  G01N33/566 ,  G01N33/68 ,  G01N33/74 ,  C07K14/695 ,  C07K7/64

CPC分类号： G01N33/5008 ,  C07K14/57509 ,  G01N33/502 ,  G01N33/566 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/74 ,  A61K38/00 ,  G01N2333/5751 ,  Y10S514/805 ,  Y10S930/26

摘要： Improved CRF antagonist peptides have the formula: ##STR1## wherein R.sub.30 is Cys or Glu; R.sub.33 is Cys, Lys or Orn; provided that when R.sub.30 is Cys, R.sub.33 is Cys and when R.sub.30 is Glu, R.sub.33 is Lys or Orn. The N-terminus may be extended by Asp-Leu-Thr. Lys may be substituted for Arg.sup.23 and its side chain connected by a lactam bridge to Glu.sup.20 to form a dicyclic peptide. Specific CRF antagonists disclosed include (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Glu.sup.30, Lys.sup.33 ]rCRF(12-41); (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Glu.sup.30, Orn.sup.33 ]rCRF(12-41), (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Cys.sup.30,33 ]rCRF (12-41) and (bicyclo 20-23,30-33) [D-Phe.sup.12, Nle.sup.21,38, Lys.sup.23,33, Glu.sup.30 ]-rCRF(12-41).

摘要翻译： 改进的CRF拮抗剂肽具有下式：（环30-33）DPheHisLeuLe​​uArgGluVal LeuGluNleAlaArgAlaGluGlnLeu LeuNleGluIleIleNH2其中R30是Cys或Glu; R33是Cys，Lys或Orn; 条件是当R30为Cys时，R33为Cys，当R30为Glu时，R33为Lys或Orn。 N末端可以被Asp-Leu-Thr延伸。 Lys可被Arg23取代，其侧链通过内酰胺桥连接至Glu20以形成双环肽。 公开的具体CRF拮抗剂包括（环30-33）[D-Phe12，Nle21,38，Glu30，Lys33] rCRF（12-41）; （环30-33）[D-Phe12，Nle21,38，Glu30，Orn33] rCRF（12-41），（环30-33）[D-Phe12，Nle21,38，Cys30,33] rCRF（12-41 ）和（双环20-23,30-33）[D-Phe12，Nle21,38，Lys23,33，Glu30] -rCRF（12-41）。

公开(公告)号：US5565574A

公开(公告)日：1996-10-15

申请号：US289103

申请日：1994-08-11

申请人： Carl A. Hoeger ,  Jean E. F. Rivier ,  John S. Porter

发明人： Carl A. Hoeger ,  Jean E. F. Rivier ,  John S. Porter

IPC分类号： A61K38/04 ,  A61K38/00 ,  C07C277/08 ,  C07C279/18 ,  C07C279/24 ,  C07C279/28 ,  C07C313/30 ,  C07D249/14 ,  C07K1/00 ,  C07K7/02 ,  C07K7/06 ,  C07K7/23

CPC分类号： C07C279/24 ,  C07C277/08 ,  C07C279/28 ,  C07C313/30 ,  C07D249/14 ,  C07K1/006 ,  C07K7/02 ,  C07K7/23 ,  A61K38/00 ,  C07C2101/14 ,  Y02P20/55

摘要： Methods of making unnatural amino acids are provided which unnatural amino acids can be incorporated into peptides which either inhibit or promote the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. These unnatural amino acids are useful in the synthesis of peptides and have the formula (a): ##STR1## where W is (CH.sub.2).sub.n or ##STR2## n is an integer from 1 to 6; j=1, 2 or 3, and preferably, Y is N--CN, X is NH and R.sub.2 is alkyl, modified alkyl, alkenyl, alkynyl, aryl or methyl pyridyl. Disclosed are peptides that are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-, 5-, 6- and/or 8-positions.

摘要翻译： 提供了制备非天然氨基酸的方法，其可将非天然氨基酸并入肽中，所述肽抑制或促进垂体腺分泌促性腺激素并抑制性腺释放类固醇。 这些非天然氨基酸可用于肽的合成并具有式（a）：其中W为（CH 2）n或 n为1至6的整数; j = 1,2或3，优选Y为N-CN，X为NH，R 2为烷基，改性烷基，烯基，炔基，芳基或甲基吡啶基。 公开了作为十肽GnRH的类似物的肽，其中在3-，5-，6-和/或8-位有至少一个非天然氨基酸残基。

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。

公开(公告)号：US5169932A

公开(公告)日：1992-12-08

申请号：US545239

申请日：1990-06-27

申请人： Carl A. Hoeger ,  Jean E. F. Rivier ,  Paula G. Theobald ,  John S. Porter ,  Catherine L. Rivier ,  Wylie W. Vale, Jr.

发明人： Carl A. Hoeger ,  Jean E. F. Rivier ,  Paula G. Theobald ,  John S. Porter ,  Catherine L. Rivier ,  Wylie W. Vale, Jr.

IPC分类号： A61K38/22 ,  A61K38/00 ,  A61K38/04 ,  C07C279/24 ,  C07C279/28 ,  C07C313/30 ,  C07D249/14 ,  C07K7/02 ,  C07K7/23 ,  C07K14/575

CPC分类号： C07K7/23 ,  C07C279/24 ,  C07C279/28 ,  C07C313/30 ,  C07D249/14 ,  C07K7/02 ,  A61K38/00 ,  C07C2101/14 ,  Y10S514/80 ,  Y10S930/11

摘要： Peptides which include unnatural amino acides and which either inhibit or promote the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such peptides that are GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. The antagonists may be used to treat steroid-dependent tumors, such as prostatic and mammary tumors. The peptides are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-position, the 5-position, the 6-position and/or the 8-position. Such unnatural amino acids are useful in the synthesis of peptides and have the formula U*: ##STR1## where n is an integer from 1 to 6; Y is N--CN, N--CONHR.sub.9, S, O or CH--NO.sub.2 ; R.sub.9 is H, Ac, lower alkyl, aromatic or heterocyclic; X is NH, O, S, M.sub.1 (CH.sub.q).sub.p M.sub.2 or M.sub.1 --(CH.sub.2).sub.p' --M.sub.2 (CH.sub.2).sub.p" --M.sub.3, where M.sub.1 is NR.sub.10, O, S or CHR.sub.3 wherein R.sub.3 is methyl, ethyl, propyl, phenyl, pyridinyl, pyrimidinyl or purinyl, q is 1 or 2; p, p' and p" are integers between O and 6; R.sub.10 is H, lower alkyl or the like, and M.sub.2 and M.sub.3 are M.sub.1, COOH, CONH.sub.2, COOR.sub.3 or CN; R.sub.1 is H, alkyl, modified alkyl, alkenyl, alkynyl, aryl or a direct bond to X; R.sub.2 is R.sub.1, OH, NH.sub.2, NHR.sub.1, or heterocycle.

摘要翻译： 包括非天然氨基酸的肽，其抑制或促进垂体分泌促性腺激素并抑制性腺释放类固醇。 施用有效量的这种肽作为GnRH拮抗剂可防止雌性哺乳动物卵的排卵和/或性腺释放类固醇。 拮抗剂可用于治疗类固醇依赖性肿瘤，例如前列腺和乳腺肿瘤。 肽是十肽GnRH的类似物，其中在3-位，5-位，6-位和/或8-位存在至少一个非天然氨基酸残基。 这种非天然氨基酸可用于肽的合成并具有式U *：其中n是1至6的整数; Y是N-CN，N-CONHR9，S，O或CH-NO2; R9是H，Ac，低级烷基，芳族或杂环基; X是NH，O，S，M1（CHq）pM2或M1-（CH2）p'-M2（CH2）p'-M3，其中M1是NR10，O，S或CHR3，其中R3是甲基，乙基，丙基 ，苯基，吡啶基，嘧啶基或嘌呤基，q为1或2; p，p'和p“是O和6之间的整数; R10为H，低级烷基等，M2和M3为M1，COOH，CONH2，COOR3或CN; R 1是H，烷基，改性烷基，链烯基，炔基，芳基或与X的直接键; R2是R1，OH，NH2，NHR1或杂环。

公开(公告)号：US5109111A

公开(公告)日：1992-04-28

申请号：US498814

申请日：1990-03-23

申请人： Jean E. F. Rivier ,  Wylie W. Vale, Jr. ,  Catherine L. Rivier ,  Jean-Francois Hernandez

发明人： Jean E. F. Rivier ,  Wylie W. Vale, Jr. ,  Catherine L. Rivier ,  Jean-Francois Hernandez

IPC分类号： A61K38/00 ,  C07K14/575

CPC分类号： C07K14/57509 ,  A61K38/00 ,  Y10S514/805 ,  Y10S530/857

摘要： Several known members of the corticotropin releasing factor (CRF) family have been synthesized and tested, including human and rat CRF which have the formula: H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His- Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln- Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met-Glu- Ile-Ile-NH.sub.2. Peptides are herein disclosed that are potent competitive antagonists of CRF in mammals. One which has been found to be particularly potent is: H-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala- Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn- Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH.sub.2. One that has shown particularly prolonged duration of potency is: H-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala- Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn- Arg-Lys-CML-Nle-Glu-Ile-Ile-NH.sub.2. These antagonists or pharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to mammals, including humans, to achieve a prevent elevation of ACTH, .beta.-endorphin, .beta.-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels and/or a lowering of brain mediated responses to stress over an extended period of time. They may also be used to affect mood, memory and learning, as well as diagnostically.

摘要翻译： 已经合成并测试了促肾上腺皮质激素释放因子（CRF）家族的几个已知成员，包括人和大鼠CRF，其具有下式：H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu- Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg- Lys-Leu-Met-Glu-Ile-Ile-NH2。 本文公开了肽，其是哺乳动物中CRF的有竞争力的拮抗剂。 已经发现特别有效的是：HD-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln -Ala-His-Ser-Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH2。 显示出特别延长的效力持续时间是：HD-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln -Ala-His-Ser-Asn-Arg-Lys-CML-Nle-Glu-Ile-Ile-NH2。 分散在药学或兽医学上可接受的液体或固体载体中的这些拮抗剂或其药学或兽医学上可接受的盐可以施用于包括人在内的哺乳动物，以达到预防ACTH，β-内啡肽，β-促渗素，其他产物 pro-opiomelanocortin基因和皮质酮水平和/或在长时间内脑介导的应激反应的降低。 它们也可能用于影响情绪，记忆和学习以及诊断。

公开(公告)号：US5064939A

公开(公告)日：1991-11-12

申请号：US475767

申请日：1990-02-06

申请人： Jean E. F. Rivier ,  Steven C. Koerber ,  Arnold T. Hagler ,  Catherine L. Rivier ,  Wylie W. Vale, Jr.

发明人： Jean E. F. Rivier ,  Steven C. Koerber ,  Arnold T. Hagler ,  Catherine L. Rivier ,  Wylie W. Vale, Jr.

IPC分类号： A61K38/24 ,  A61K38/00 ,  C07K1/04 ,  C07K1/113 ,  C07K7/23 ,  C07K14/575

CPC分类号： C07K7/23 ,  A61K38/00

摘要： Peptides which inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. These peptides may be used to treat steroid-dependent tumors, such as prostatic and mammary tumors. The peptides include cyclic, bicyclic and tricyclic analogs of the decapeptide GnRH, and preferably there are at least two covalent bonds between the residues in the 4- and 10-positions, the residues in the 5- and 8-positions and the residues in the 1- and 3-positions, respectively. Examples of such bonds include a disulfide linkage between Cys residues, an amide linkage between a side chain amino group and a side chain carboyxl group, a dicarba linkage between side-chain alkyl groups, and a carba linkage between a side-chain alkyl group and a side-chain sulfhydryl group.

摘要翻译： 抑制垂体分泌促性腺激素并抑制性腺释放类固醇的肽。 施用有效量的这种GnRH拮抗剂防止雌性哺乳动物卵的排卵和/或性腺释放类固醇。 这些肽可用于治疗类固醇依赖性肿瘤，例如前列腺和乳腺肿瘤。 肽包括十肽GnRH的环状，双环和三环类似物，并且优选在4-和10-位残基之间存在至少两个共价键，5-和8-位中的残基和 分别为1-和3-位。 这种键的实例包括Cys残基之间的二硫键，侧链氨基和侧链羰基之间的酰胺键，侧链烷基之间的二氨键，侧链烷基与侧链烷基之间的连接 侧链巯基。

公开(公告)号：US5032507A

公开(公告)日：1991-07-16

申请号：US120470

申请日：1987-11-13

申请人： John Yu ,  Alice L. Yu ,  Joan Vaughan ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

发明人： John Yu ,  Alice L. Yu ,  Joan Vaughan ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

IPC分类号： A61K38/00 ,  A61K38/04 ,  A61K38/22 ,  A61P7/00 ,  C07K14/435 ,  C07K14/575

CPC分类号： A61K38/22 ,  Y10S435/81

摘要： A method for modulating the rate of erythropoiesis in human hematopoietic progenitor cells. FRP is found to be an efficacious potentiator of, and inhibin a suppressor of, erythropoietin-induced differentiation. FRP and inhibin are shown to be functional antagonists of each other, and thus represent an effective means for modulating erythropoiesis in a number of disease states which are directly caused by or associated with an abnormal rate of erythropoiesis.

摘要翻译： 调节人类造血祖细胞中红细胞生成速率的方法。 发现FRP是促红细胞生成素诱导分化的有效增效剂，抑制抑制素。 FRP和抑制素显示为彼此的功能性拮抗剂，因此代表了直接由异常红细胞生成速率引起或与之相关的许多疾病状态调节红细胞生成的有效手段。

公开(公告)号：US5026685A

公开(公告)日：1991-06-25

申请号：US219596

申请日：1988-07-15

申请人： Jaroslav H. Boublik ,  Jean E. F. Rivier ,  Marvin R. Brown ,  Neal A. Scott

发明人： Jaroslav H. Boublik ,  Jean E. F. Rivier ,  Marvin R. Brown ,  Neal A. Scott

IPC分类号： A61K38/00 ,  C07K14/575

CPC分类号： C07K14/57545 ,  A61K38/00

摘要： Human Neuropeptide Y(NPY) has the formula: H-Tyr-Pro-Ser-Lys-Pro-Asp-Asn-Pro-Gly-Glu-Asp-Ala- Pro-Ala-Glu-Asp-Met-Ala-Arg-Tyr-Tyr-Ser-Ala-Leu-Arg-His-Tyr- Ile-Asn-Leu-Ile-Thr-Arg-Gln-Arg-Tyr-NH.sub.2. Porcine and rat NPY have the same sequence except for Leu instead of Met in the 17-position. Porcine PYY is homologous having 11 different residues. NPY analogs wherein the N-terminus is shortened and which may contain one or more specific subsitutions for the naturally occurring residues, or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals, including humans, to substantially lower blood pressure over an extended period of time or to counteract hypertension.

摘要翻译： 人神经肽Y（NPY）具有下式：H-Tyr-Pro-Ser-Lys-Pro-Asp-Asn-Pro-Gly-Glu-Asp-Ala- Pro-Ala-Glu-Asp-Met-Ala-Arg- Tyr-Tyr-Ser-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu-Ile-Thr-Arg-Gln-Arg-Tyr-NH2。 猪和大鼠NPY具有相同的序列，除了Leu而不是17位的Met。 猪PYY具有11个不同残基的同源物。 NPY类似物，其中N末端被缩短并且可以含有分散在药学上可接受的液体或固体载体中的天然存在的残基或其药学上可接受的盐的一个或多个特异性亚基，可以包括人哺乳动物 在较长时间内显着降低血压或抵抗高血压。

公开(公告)号：US5002931A

公开(公告)日：1991-03-26

申请号：US53235

申请日：1987-05-22

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

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

IPC分类号： A61K38/00 ,  A61K38/04 ,  A61K38/25 ,  A61P5/00 ,  A61P15/00 ,  A61P35/00 ,  A61P43/00 ,  C07K14/00 ,  C07K14/575 ,  C07K14/60 ,  C07K14/61

CPC分类号： C07K14/60 ,  A61K38/00

摘要： The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals, including humans, which have resistance to enzymatic degradation in the body, and which have the sequence: (B)R.sub.1 -R.sub.2 -R.sub.3 -Ala-Ile-Phe-Thr-R.sub.8 -Ser-(Q.sub.1)R.sub.10 - Arg-R.sub.12. (Q.sub.2)R.sub.13 -Leu-R.sub.15 -Gln-Leu-Ser-(Q.sub.3)Ala-Arg. R.sub.21 -(Q.sub.4)R.sub.22 -Leu-Gln-Asp-Ile-R.sub.27 -R.sub.28 -Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-R.sub.42 -R.sub.43 -R.sub.44 wherein R.sub.1 is Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His or D-His; B is H, C.sup.a Me, N.sup.a Me, desamino, Ac or For; R.sub.2 is Ala, D-Ala, NMA or D-NMA; R.sub.3 is Asp or D-Asp; R.sub.8 is Ser, Asn, Lys, Arg, Asp or Gln; R.sub.10 is Tyr, D-Tyr or Phe; R.sub.12 is Arg or Lys; R.sub.13 is Ile, Val, Leu or Ala; R.sub.15 is Gly or Ala; R.sub.21 is Lys, D-Lys or D-Arg; R.sub.22 is Leu, Ile, Ala or Val; R.sub.27 is Met, D-Met, Ala, Nle, Ile, Leu, Nva or Val; R.sub.28 is Asn or Ser; R.sub.42 is Phe, Ala or Val; R.sub.43 is Asn or Arg; R.sub.44 is a natural amino acid; Q.sub.1 -Q.sub.4 are either H or C.sup.a Me, provided however that any or all of the residues between R.sub.30 and R.sub.44, inclusive, may be deleted.These peptides as well as their nontoxic salts may also be used diagnostically.