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1. 发明授权

US09035022B2 Cyclic CRF antagonist peptides 有权
标题翻译：循环CRF拮抗肽
公开(公告)号：US09035022B2
公开(公告)日：2015-05-19
申请号：US13996186
申请日：2011-12-22
申请人： Jean E. F. Rivier
发明人： Jean E. F. Rivier
IPC分类号： A61K38/00 , C07K14/47 , C07K14/575
CPC分类号： C07K14/47 , A61K38/00 , C07K14/57509
摘要： Cyclic CRF antagonist peptides having improved properties of “drugability”. The peptides are 33 residues in length with a lactam bond between the residues in position 22 and 25; however, they may be N-terminally shortened by up to 3 residues.
摘要翻译：循环CRF拮抗剂肽具有改善的“药物性”性质。所述肽的长度为33个残基，位置22和25之间的残基之间具有内酰胺键; 然而，它们可以被N末端缩短多达3个残基。

2. 发明授权

US08691761B2 Somatostatin receptor 2 antagonists 有权
标题翻译：生长抑素受体2拮抗剂
公开(公告)号：US08691761B2
公开(公告)日：2014-04-08
申请号：US12104318
申请日：2008-04-16
申请人： Jean E. F. Rivier , Judit Erchegyi , Jean Claude Reubi , Helmut R. Maecke
发明人： Jean E. F. Rivier , Judit Erchegyi , Jean Claude Reubi , Helmut R. Maecke
IPC分类号： A61K38/31 , A61P3/10
CPC分类号： C07K14/655 , A61K38/00 , G01N2333/655
摘要： The invention is directed to somatostatin analogs which are receptor antagonists of the somatostatin receptor, including receptor-selective antagonists, especially sst2-selective antagonists. Related compounds and compositions are included, including antagonists complexed with or conjugated to radioactive nuclides. The antagonists of the invention are useful in diagnosing and treating neoplastic and non-neoplastic mammalian diseases; such methods, and kits, are encompassed.
摘要翻译：本发明涉及作为生长抑素受体的受体拮抗剂的生长抑素类似物，包括受体选择性拮抗剂，特别是sst2选择性拮抗剂。包括相关化合物和组合物，包括与放射性核素复合或缀合的拮抗剂。本发明的拮抗剂可用于诊断和治疗肿瘤和非肿瘤性哺乳动物疾病; 包括这些方法和试剂盒。

3. 发明授权

US08501687B2 Receptor(SSTR2)-selective somatostatin antagonists 有权
标题翻译：受体（SSTR2） - 选择性生长抑素拮抗剂
公开(公告)号：US08501687B2
公开(公告)日：2013-08-06
申请号：US13159020
申请日：2011-06-13
申请人： Jean E. F. Rivier , Judit Erchegyi , Jean Claude Reubi , Helmut R. Maecke
发明人： Jean E. F. Rivier , Judit Erchegyi , Jean Claude Reubi , Helmut R. Maecke
IPC分类号： A61K38/31 , A61K3/10 , A61K7/12
CPC分类号： C07K14/655 , A61K38/00
摘要： SRIF peptide antagonists, which are selective for SSTR2 in contrast to the other cloned SRIF receptors and which bind with high affinity to the cloned human receptor SSTR2 but do not activate the receptor, have many useful functions. Because they do not bind with significant affinity to SSTR1, SSTR3, SSTR4 or SSTR5, their administration avoids potential undesirable side effects. By incorporating radioiodine or the like in these SSTR2-selective SRIF antagonists, a labeled compound useful in drug-screening methods is provided. Alternatively, for use in therapy, highly radioactive moieties can be N-terminally coupled, complexed or chelated thereto. Because they block the receptor function, they can be used therapeutically to block certain physiological effects which SSTR2 mediates.
摘要翻译：与其他克隆的SRIF受体相比，SRIF肽拮抗剂对于SSTR2是选择性的，并且与克隆的人受体SSTR2以高亲和力结合但不激活受体具有许多有用的功能。因为它们不与SSTR1，SSTR3，SSTR4或SSTR5具有显着的亲合力结合，所以它们的给药避免了潜在的不良副作用。通过在这些SSTR2选择性SRIF拮抗剂中引入放射性碘等，提供了可用于药物筛选方法的标记化合物。或者，为了在治疗中使用，高度放射性的部分可以与其N-末端偶联，复合或螯合。因为它们阻断受体功能，它们可以用于治疗性地阻断SSTR2介导的某些生理作用。

4. 发明授权

US07960342B2 Receptor(SSTR2)-selective somatostatin antagonists 有权
标题翻译：受体（SSTR2） - 选择性生长抑素拮抗剂
公开(公告)号：US07960342B2
公开(公告)日：2011-06-14
申请号：US11872367
申请日：2007-10-15
申请人： Jean E. F. Rivier , Judit Erchegyi , Jean Claude Reubi , Helmut R. Maecke
发明人： Jean E. F. Rivier , Judit Erchegyi , Jean Claude Reubi , Helmut R. Maecke
IPC分类号： A61K38/18 , A61K38/31
CPC分类号： C07K14/655 , A61K38/00
摘要： SRIF peptide antagonists, which are selective for SSTR2 in contrast to the other cloned SRIF receptors and which bind with high affinity to the cloned human receptor SSTR2 but do not activate the receptor, have many useful functions. Because they do not bind with significant affinity to SSTR1, SSTR3, SSTR4 or SSTR5, their administration avoids potential undesirable side effects. Because they block the receptor function, they can be used therapeutically to block certain physiological effects which SSTR2 mediates. By incorporating radioiodine or the like in these SSTR2-selective SRIF antagonists, a labeled compound useful in drug-screening methods is provided. Alternatively, for use in therapy, highly radioactive moieties can be N-terminally coupled, complexed or chelated thereto.
摘要翻译：与其他克隆的SRIF受体相比，SRIF肽拮抗剂对SSTR2具有选择性，并且与克隆的人受体SSTR2具有高亲和力但不激活受体的结合具有许多有用的功能。因为它们不与SSTR1，SSTR3，SSTR4或SSTR5具有显着的亲合力结合，所以它们的给药避免了潜在的不良副作用。因为它们阻断受体功能，它们可以用于治疗性地阻止SSTR2介导的某些生理作用。通过在这些SSTR2选择性SRIF拮抗剂中引入放射性碘等，提供了可用于药物筛选方法的标记化合物。或者，为了在治疗中使用，高度放射性的部分可以与其N-末端偶联，复合或螯合。

5. 发明授权

US07019109B2 SSTR1-selective analogs 失效
标题翻译： SSTR1选择性类似物
公开(公告)号：US07019109B2
公开(公告)日：2006-03-28
申请号：US10099240
申请日：2002-03-15
申请人： Jean E. F. Rivier , Jean Claude Reubi
发明人： Jean E. F. Rivier , Jean Claude Reubi
IPC分类号： C07K7/665 , C07K7/64
CPC分类号： C07K14/6555 , A61K51/083 , A61K51/088
摘要： Analogs of SRIF which are selective for SSTR1 in contrast to the other cloned SRIF receptors. These analogs are useful in determining the tissue and cellular expression of the receptor SSTR1 and its biological role in the endocrine, exocrine and nervous system, as well as in regulating tumor growth. SRIF analog peptides, such as des-AA1,2,5[D-Trp8, NαMeIAmp9, Tyr11]-SRIF and counterparts incorporating Cbm at the N-terminus and/or NαSer13, inhibit the binding of a universal SRIF radioligand to the cloned human receptor SSTR1, but they do not bind with significant affinity to human SSTR2, SSTR3, SSTR4 or SSTR5. By incorporating an iodinated tyrosine in position-2 or in position-11 in these SSTR1-selective SRIF analogs, a labeled compound useful in drug-screening methods is provided. The N-terminus accommodates bulky moieties without loss of selectivity, and a carbamoyl moiety or a conjugating agent that will accept a radioactive nuclide or will link to a cytotoxin may be present at the N-terminus.
摘要翻译：与其他克隆的SRIF受体相反，SRIF的选择性为SSTR1的类似物。这些类似物可用于确定受体SSTR1的组织和细胞表达及其在内分泌，外分泌和神经系统中的生物学作用以及调节肿瘤生长。 SRIF类似物肽，例如des-AA 12,5，D-Trp 8，Nα，Me 3， SUP>，Tyr 11] - SRIF和在N末端和/或NαSer 13结合Cbm的对应物抑制结合与克隆的人受体SSTR1通用的SRIF放射配体，但它们不以与人SSTR2，SSTR3，SSTR4或SSTR5的显着亲和力结合。通过在这些SSTR1选择性SRIF类似物中掺入位置2或位置-11的碘化酪氨酸，提供了可用于药物筛选方法的标记化合物。 N-末端可容纳大量的部分而不损失选择性，并且可以在N-末端存在将接受放射性核素或将连接至细胞毒素的氨基甲酰基部分或共轭试剂。

6. 发明授权

US5710249A Amino acids and processes for making peptides using same 失效
标题翻译：氨基酸和使用其制备肽的方法
公开(公告)号：US5710249A
公开(公告)日：1998-01-20
申请号：US465854
申请日：1995-06-06
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 , C07K2/00
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) 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是（CH 2）或 n是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-位存在至少一个非天然氨基酸的残基。

7. 发明授权

US5580957A GnRH analogs 失效
标题翻译： GnRH类似物
公开(公告)号：US5580957A
公开(公告)日：1996-12-03
申请号：US210619
申请日：1994-03-18
申请人： Carl A. Hoeger , Jean E. F. Rivier , Paula G. Theobald , John S. Porter
发明人： Carl A. Hoeger , Jean E. F. Rivier , Paula G. Theobald , John S. Porter
IPC分类号： A61K38/00 , C07C277/08 , C07C279/24 , C07C279/28 , C07C313/30 , C07D249/14 , C07K7/02 , C07K7/23 , C07K14/695
CPC分类号： C07C277/08 , C07C279/24 , C07C279/28 , C07C313/30 , C07D249/14 , C07K7/02 , C07K7/23 , A61K38/00 , C07C2101/14
摘要： Peptides which include unnatural amino acids and which either promote or 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 peptides that are GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads and may be used to treat steroid-dependent tumors. The agonists can be used for control of reproduction processes, to treat precocious puberty, endometriosis, and the like. The peptides 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. Unnatural amino acids having the following formula are incorporated in a preferred group of synthesized peptides: ##STR1## Methods for synthesizing such peptides having the triazole side chains are disclosed wherein one side chain modification (or two simultaneously) is carried out on an amino-substituted phenylalanine residue in a peptide chain which is a part of a peptidoresin.
摘要翻译：包括非天然氨基酸并且促进或抑制垂体分泌促性腺激素并抑制性腺释放类固醇的肽。施用有效量的这种肽作为GnRH拮抗剂可防止雌性哺乳动物卵的排卵和/或由性腺释放类固醇，并可用于治疗类固醇依赖性肿瘤。激动剂可用于控制繁殖过程，治疗早熟青春期，子宫内膜异位症等。肽是十肽GnRH的类似物，其中在3-，5-，6-和/或8-位有至少一个非天然氨基酸残基。具有下列结构式的非天然氨基酸被掺入优选的合成肽组中：具有j = 1,2或3的合成肽。公开了合成具有三唑侧链的肽的方法，其中一个侧链修饰（或两个同时）在作为肽聚糖树脂的一部分的肽链中的氨基取代的苯丙氨酸残基上进行。

8. 发明授权

US5506207A GNRH antagonists XIII 失效
标题翻译： GNRH拮抗剂十三
公开(公告)号：US5506207A
公开(公告)日：1996-04-09
申请号：US210627
申请日：1994-03-18
申请人： Jean E. F. Rivier , John S. Porter , Carl A. Hoeger , Guangcheng Jiang , Catherine L. Rivier
发明人： Jean E. F. Rivier , John S. Porter , Carl A. Hoeger , Guangcheng Jiang , Catherine L. Rivier
IPC分类号： A61K38/00 , A61P13/02 , A61P15/00 , A61P29/00 , A61P31/12 , A61P35/00 , A61P37/04 , C07K7/06 , C07K7/23 , A61K38/04 , C07K7/00
CPC分类号： C07K7/23 , A61K38/00
摘要： Analogs of the decapeptide GnRH which include two significantly modified amino acids at positions 5 and 6 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 and may be used to treat steroid-dependent tumors. Particularly effective peptides which are soluble in water at physiologic pH and which have a low tendency to gel when administered in vivo have the following formula:Ac-.beta.-D-2NAL-(4Cl)D-Phe-D-3PAL-Ser-Aph(Q.sub.1)(3-amino-1,2,4 triazole)-D-Aph(Q.sub.2)(3-amino 1,2,4-triazole)-Leu-Lys (isopropyl)-Pro-D-Ala-NH.sub.2,where Q.sub.1 and Q.sub.2 are amino acids, such as Gly, .beta.-Ala, Ala, D-Ala, Ser, Aib, Ahx and Gab. Examples of other GnRH antagonists includeAc-.beta.-D-2NAL-(4Cl)D-Phe-D-3PAL-Ser-Aph(Atz)-D-Aph(Ac)-Leu-Lys(isopropyl)-Pro-D-Ala-NH.sub.2,Ac-.beta.-D-2NAL-(4Cl)D-Phe-D-3PAL-Ser-Aph(.beta.-Ala)(3-amino-1,2,4 triazole)-D-Aph(.beta.-Ala)(3-amino-1,2,4 triazole)-Leu-Lys(isopropyl)-Pro-D-Ala-NH.sub.2,Ac-.beta.-D-2NAL-(4Cl)D-Phe-D-3PAL-Ser-Aph(Ac-D-Ser)-D-Aph(Ac-D-Ser)-Leu-Lys(isopropyl)-Pro-D-Ala-NH.sub.2, andAc-.beta.-D-2NAL-(4Cl)D-Phe-D-3PAL-Ser-Aph(Ac)-D-Aph(Ac)-Leu-Lys(isopropyl)-Pro-D-Ala-NH.sub.2.
摘要翻译：包括位置5和6在内的两个显着修饰的氨基酸的十肽GnRH的类似物抑制垂体腺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GnRH拮抗剂防止雌性哺乳动物卵的排卵和/或由性腺释放类固醇，并可用于治疗类固醇依赖性肿瘤。 Ac-β-D-2NAL-（4Cl）D-Phe-D-3PAL-Ser-Aph在生理pH下可溶于水的并且在体内施用时具有低凝胶倾向的特别有效的肽具有下式：（Q1）（3-氨基-1,2,4-三唑）-D-Aph（Q2）（3-氨基-1,2,4-三唑）-Leu-Lys（异丙基）-Pro-D-Ala-NH 2，其中Q1和Q2是氨基酸，例如Gly，β-Ala，Ala，D-Ala，Ser，Aib，Ahx和Gab。其他GnRH拮抗剂的实例包括Ac-β-D-2NAL-（4Cl）D-Phe-D-3PAL-Ser-Aph（Atz）-D-Aph（Ac）-Leu-Lys（异丙基） Ala-NH2，Ac-β-D-2NAL-（4Cl）D-Phe-D-3PAL-Ser-Aph（β-Ala）（3-氨基-1,2,4-三唑）-D-Aph（β- Ala）（3-氨基-1,2,4-三唑）-Leu-Lys（异丙基）-Pro-D-Ala-NH 2，Ac-β-D-2NAL-（4Cl）D-Phe-D-3PAL-Ser （Ac-D-Ser）-D-Aph（Ac-D-Ser）-Leu-Lys（异丙基）-Pro-D-Ala-NH 2和Ac-β-D-2NAL-（4Cl） Phe-D-3PAL-Ser-Aph（Ac）-D-Aph（Ac）-Leu-Lys（异丙基）-Pro-D-Ala-NH 2。

9. 发明授权

US5049655A Melanin-concentrating hormones 失效
标题翻译：黑色素浓缩激素
公开(公告)号：US5049655A
公开(公告)日：1991-09-17
申请号：US326984
申请日：1989-03-22
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
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。

10. 发明授权

US4737578A Human inhibin 失效
标题翻译：人抑制素
公开(公告)号：US4737578A
公开(公告)日：1988-04-12
申请号：US848924
申请日：1986-04-07
申请人： Ronald M. Evans , Michael G. Rosenfeld , Gail Cerelli , Kelly E. Mayo , Joachim Spiess , Jean E. F. Rivier , Wylie W. Vale, Jr.
发明人： Ronald M. Evans , Michael G. Rosenfeld , Gail Cerelli , Kelly E. Mayo , Joachim Spiess , Jean E. F. Rivier , Wylie W. Vale, Jr.
IPC分类号： A61K38/00 , C07K14/575 , C07K7/10 , C07K13/00
CPC分类号： C07K14/575 , A61K38/00 , Y10S930/26
摘要： Proteins with inhibin activity having a weight of about 32,000 daltons. The molecule 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. The 18K chain is obtained from the human inhibin gene and has the formula: H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu-Gln-Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Leu-Asn-Ile-Ser-Phe-Gln-Glu-Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R.sub.65 -Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His-Ile-Pro-Pro-Asn-Leu-Ser-Leu-Pro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly-Ala-Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pro-Leu-His-Val-Arg-Thr-Thr-Ser-Asp-Gly-Gly-Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH, wherein R.sub.65 is Ile or Arg. The 18K chain is connected by disulfide bonding to the 14K chain.
摘要翻译：具有约32,000道尔顿重量的具有抑制素活性的蛋白质。该分子由分子量分别为约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。 18K链由人抑制素基因得到，具有下式：H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu Gln-Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Le-Asn-Ile-Ser-Phe-Gln-Glu- Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R65-Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His- Ile-Pro-Pro-As n-Leu-Ser-Leu-Pro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly -Ala-Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pr-Leu-His-Val-Arg-Thr-Thr-Ser-Asp-Gly-Gly- Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH，其中R65是Ile或Arg。 18K链通过二硫键与14K链连接。

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