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31. 发明授权

US4386074A LRF Antagonists 失效
标题翻译： LRF拮抗剂
公开(公告)号：US4386074A
公开(公告)日：1983-05-31
申请号：US287189
申请日：1981-07-27
申请人： Wylie W. Vale, Jr. , Jean E. F. Rivier
发明人： Wylie W. Vale, Jr. , Jean E. F. Rivier
IPC分类号： A61K38/00 , C07K7/16 , C07K7/23 , A61K37/00 , C07C103/52
CPC分类号： C07K7/16 , C07K7/23 , A61K38/00 , Y10S514/80 , Y10S930/13
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 prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. The peptides have the structure:R.sub.1 -dehydro Pro-R.sub.2 -D-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH.sub.2wherein R.sub.1 is selected from the group consisting of hydrogen, formyl, acetyl, acrylyl, benzoyl and allyl; R.sub.2 is selected from the group consisting dichloro-D-Phe, C.sup..alpha. Me4Cl-D-Phe, (CH.sub.3).sub.5 -D-Phe, CF.sub.3 -D-Phe, F-D-Phe, difluoro-D-Phe, AcNH-D-Phe, NO.sub.2 -D-Phe, dinitro-D-Phe, Br-D-Phe, dibromo-D-Phe, CH.sub.3 S-D-Phe, OCH.sub.3 -D-Phe and CH.sub.3 -D-Phe, wherein any D-isomer amino acid can be substituted for D-Trp in the 6-position, and wherein N.sup..alpha. MeLeu may be substituted for Leu.
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。施用有效量防止雌性哺乳动物卵的排卵和/或性腺释放类固醇。肽具有以下结构：R1-脱氢Pro-R2-D-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2，其中R1选自氢，甲酰基，乙酰基，丙烯酰基，苯甲酰基和烯丙基; R2选自二氯-D-Phe，CαMe4Cl-D-Phe，（CH3）5-D-Phe，CF3-D-Phe，FD-Phe，二氟-D-Phe，AcNH-D- Phe，NO 2 -D-Phe，二硝基-D-Phe，Br-D-Phe，二溴-D-Phe，CH3S-D-Phe，OCH3-D-Phe和CH3-D-Phe，其中任何D-异构体氨基酸可以代替6位的D-Trp，并且其中NαMeLeu可以代替Leu。

32. 发明授权

US4307083A LRF Antagonists 失效
标题翻译： LRF拮抗剂
公开(公告)号：US4307083A
公开(公告)日：1981-12-22
申请号：US147555
申请日：1980-05-08
申请人： Jean E. F. Rivier , Catherine L. Rivier , Wylie W. Vale, Jr.
发明人： Jean E. F. Rivier , Catherine L. Rivier , Wylie W. Vale, Jr.
IPC分类号： A61K38/00 , C07K7/16 , C07K7/23 , A61K37/00 , C07C103/52
CPC分类号： C07K7/23 , C07K7/16 , A61K38/00 , Y10S514/80 , Y10S930/13
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 prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. The peptides have the structure:R.sub.1 -R.sub.2 -R.sub.3 -Ser-Tyr-R.sub.4 -R.sub.5 -Arg-R.sub.6wherein R.sub.1 is selected from the group consisting of dehydro Pro, dehydro D-Pro, Acetyl dehydro Pro and acetyl dehydro D-Pro; R.sub.2 is selected from the group consisting of D-Phe, Phe, N.alpha.Me-Phe, His, D-His, D-Trp, Trp and N.alpha.Me-Leu; R.sub.3 is selected from the group consisting of D-Trp, Trp D-Phe, Phe, Pro and D-His; R.sub.4 is selected from the group consisting of Gly, D-Trp, D-Phe, imBzl-D-His and D-Tyr; R.sub.5 is selected from the group consisting of Leu and N.alpha.Me-Leu; and R.sub.6 is selected from the group consisting of Pro-Gly-NH.sub.2 and Pro-NH-CH.sub.2 -CH.sub.3.
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。施用有效量防止雌性哺乳动物卵的排卵和/或性腺释放类固醇。肽具有以下结构：R1-R2-R3-Ser-Tyr-R4-R5-Arg-R6，其中R1选自脱氢Pro，脱氢D-Pro，乙酰脱氢Pro和乙酰基脱氢D-Pro; R2选自D-Phe，Phe，NαMe-Phe，His，D-His，D-Trp，Trp和NαMe-Leu; R3选自D-Trp，Trp D-Phe，Phe，Pro和D-His; R4选自Gly，D-Trp，D-Phe，imBzl-D-His和D-Tyr; R5选自Leu和NαMe-Leu; 并且R 6选自Pro-Gly-NH 2和Pro-NH-CH 2 -CH 3。

33. 发明授权

US4292313A LRF Antagonists 失效
标题翻译： LRF拮抗剂
公开(公告)号：US4292313A
公开(公告)日：1981-09-29
申请号：US140487
申请日：1980-04-15
申请人： Wylie W. Vale, Jr. , Jean E. F. Rivier
发明人： Wylie W. Vale, Jr. , Jean E. F. Rivier
IPC分类号： A61K38/04 , A61K38/00 , A61P13/02 , A61P15/00 , C07K7/16 , C07K7/23 , C07K14/575 , A61K37/00 , C07C103/52
CPC分类号： C07K7/16 , C07K7/23 , A61K38/00 , Y10S514/809 , Y10S930/13
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 prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. The peptides have the structure:R.sub.1 -R.sub.2 -pCl-D-Phe-D-Trp-Ser-Tyr-R.sub.3 -R.sub.4 -Arg-Pro-R.sub.5wherein R.sub.1 is selected from the group consisting of hydrogen, formyl, acetyl, acrylyl, benzoyl and allyl; R.sub.2 is selected from the group consisting of dehydro Pro, dehydro D-Pro, Thz and D-Thz; R.sub.3 is selected from the group consisting of D-Trp and (imBzl)D-His; R.sub.4 is selected from the group consisting of Leu and N.sup..alpha. MeLeu; and R.sub.5 is selected from the group consisting of Gly-NH.sub.2 and NHCH.sub.2 CH.sub.3.
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。施用有效量防止雌性哺乳动物卵的排卵和/或性腺释放类固醇。肽具有以下结构：R1-R2-pCl-D-Phe-D-Trp-Ser-Tyr-R3-R4-Arg-Pro-R5，其中R1选自氢，甲酰基，乙酰基，丙烯酰基，苯甲酰基和烯丙基; R2选自脱氢Pro，脱氢D-Pro，Thz和D-Thz; R3选自D-Trp和（imBz1）D-His; R4选自Leu和NαMeLeu; 并且R 5选自Gly-NH 2和NHCH 2 CH 3。

34. 发明授权

US4211693A Peptides with para-substituted phenylalanine 失效
标题翻译：具有对位取代苯丙氨酸的肽
公开(公告)号：US4211693A
公开(公告)日：1980-07-08
申请号：US967505
申请日：1978-12-07
申请人： Jean E. F. Rivier , Marvin R. Brown , Wylie W. Vale, Jr.
发明人： Jean E. F. Rivier , Marvin R. Brown , Wylie W. Vale, Jr.
IPC分类号： A61K38/00 , C07K14/655 , C07C103/52 , A61K37/00
CPC分类号： C07K14/6555 , A61K38/00 , Y10S514/806 , Y10S930/16
摘要： Somatostatin peptides are modified by substitution of para-methoxylated Phe or para-halogenated Phe for any Phe in the peptide. The modified somatostatin peptide analogs have the formulae: ##STR1## wherein R is hydrogen or an acyl group; R.sub.1 is selected from the group consisting of Lys or Des R.sub.1 ; R.sub.2 is selected from the group consisting of Asn, Ala or Des R.sub.2. The amino acids of the R.sub.2 group can be either the L-form or the D-form; R.sub.3 is selected from the group consisting of Trp or D-Trp; R.sub.4 is selected from the group consisting of Thr or Des R.sub.4 ; R.sub.5 is selected from the group consisting of Ser, D-Ser, Phe, X or Des R.sub.5 ; and X is selected from the group consisting of Phe, para-halogenated Phe and para-methoxylated Phe. Provided that at least one X is either para-halogenated Phe or para-methoxylated Phe.
摘要翻译：通过将肽中的任何Phe取代对甲氧基化的Phe或对位卤代Phe来修饰生长抑素肽。修饰的生长抑素肽类似物具有下式：其中R是氢或酰基; R1选自Lys或Des R1; R2选自Asn，Ala或Des R2。 R2基团的氨基酸可以是L型或D型; R3选自Trp或D-Trp; R4选自Thr或Des R4; R5选自Ser，D-Ser，Phe，X或Des R5; X选自Phe，对位卤化Phe和对甲氧基化Phe。条件是至少一个X是对位卤化Phe或对甲氧基化的Phe。

35. 发明授权

US4133782A Somatostatin analogs with dissociated biological activities 失效
标题翻译：具有离解生物活性的生长抑素类似物
公开(公告)号：US4133782A
公开(公告)日：1979-01-09
申请号：US785533
申请日：1977-04-07
申请人： Wylie W. Vale, Jr. , Jean E. F. Rivier , Marvin R. Brown
发明人： Wylie W. Vale, Jr. , Jean E. F. Rivier , Marvin R. Brown
IPC分类号： A61K38/00 , C07K14/655 , C08L37/00 , C07C103/52
CPC分类号： C07K14/6555 , A61K38/00 , Y10S930/12 , Y10S930/16
摘要： The present invention relates to peptides having dissociated biological activity in respect to the inhibition of growth hormone, insulin, and glucagon secretion. The peptides are analogs of somatostatin.
摘要翻译：本发明涉及在抑制生长激素，胰岛素和胰高血糖素分泌方面具有解离生物活性的肽。肽是生长抑素的类似物。

36. 发明授权

US07851588B2 CRFR1 selective ligands 有权
标题翻译： CRFR1选择性配体
公开(公告)号：US07851588B2
公开(公告)日：2010-12-14
申请号：US12366816
申请日：2009-02-06
申请人： Jean E. F. Rivier , Wylie W. Vale, Jr. , Marilyn H. Perrin , Jozsef Gulyas
发明人： Jean E. F. Rivier , Wylie W. Vale, Jr. , Marilyn H. Perrin , Jozsef Gulyas
IPC分类号： A61K38/12
CPC分类号： C07K14/47 , A61K38/00 , C07K14/57509
摘要： CRF peptide analogs that bind to CRFR1 with an affinity far greater than they bind to CRFR2. Some of these analogs exhibit CRF agonist activity. One exemplary analog that may be made by solid-phase synthesis is:(cyclo 31-34)[Ac-Pro4,D-Phe12,Nle18,21,Glu31,Lys34]-sucker urotensin(4-41).
摘要翻译：结合CRFR1的CRF肽类似物的亲和力远远大于它们与CRFR2结合的亲和力。这些类似物中的一些表现出CRF激动剂活性。可以通过固相合成制备的一个示例性类似物是：（环31-34）[Ac-Pro4，D-Phe12，Nle18,21，Glu31，Lys34]刺激性尿素转运蛋白（4-41）。

37. 发明授权

US5169932A GnRH analogs 失效
标题翻译： GNRH模拟
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。

38. 发明授权

US5109111A CRF antagonists 失效
标题翻译： CRF拮抗剂
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。

39. 发明授权

US5064939A Cyclic GnRH antagonists 失效
标题翻译：循环GNRH拮抗剂
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。

40. 发明授权

US5002931A GRF analogs VII 失效
标题翻译： GRF类似物VII
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.

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