公开(公告)号：US4490364A

公开(公告)日：1984-12-25

申请号：US522846

申请日：1983-08-12

申请人： Jean E. F. Rivier ,  Botond Penke

发明人： Jean E. F. Rivier ,  Botond Penke

IPC分类号： A61K38/00 ,  C07K14/595 ,  A61K37/00 ,  C07C103/52

CPC分类号： C07K14/5955 ,  A61K38/00

摘要： Analogs of CCK(1-8) having dissociated activity with respect to stimulating the contraction of the gall bladder and arresting the secretion of gastric acid. Various analogs also exhibit improved anticonvulsive potency. The peptides are characterized by the following formula:X--R.sub.0 --R.sub.1 --Tyr(Y)--R.sub.3 --R.sub.4 --Trp--R.sub.6 --R.sub.7 --R.sub.8 --NHQwherein X is H, Suc, Ac, Oxa, Mal, Glt, Prp, Prl or Acr; R.sub.0 is Gln, pGlu, Cys, Tyr, Tyr(OCH.sub.3), des--NH.sub.2 --Tyr or desR.sub.0 ; R.sub.1 is Asp, Tyr(OH or SE), Ser(OH or SE), Hyp(OH or SE), Thr(OH or SE), Cys, Tyr(OCH.sub.3) or desR.sub.1 ; Y is OH or SE; R.sub.3 is Met, Nva or Nle; R.sub.4 is Gly, D--Cys or D--Ala; R.sub.6 is Met, Nva or Nle; R.sub.7 is Asp, Ser(SE), Thr(SE) or Hyp(SE); R.sub.8 is Phe or Tyr(OCH.sub.3); and Q is lower alkyl, fluoro lower alkyl or hydrogen; provided that when R.sub.3 and R.sub.6 are Met and R.sub.7 is Asp then R.sub.4 is D--Ala. A pharmaceutically acceptable salt thereof may also be employed.

摘要翻译： CCK（1-8）的类似物具有相对于刺激胆囊收缩和阻止胃酸分泌的离解活性。 各种类似物也表现出改善的抗惊厥药效。 肽通过下式表征：X-R0-R1-Tyr（Y）-R3-R4-Trp-R6-R7-R8-NHQ其中X是H，Suc，Ac，Oxa，Mal，Glt，Prp， Prl或Acr; R0是Gln，pGlu，Cys，Tyr，Tyr（OCH3），des-NH2-Tyr或desR0; R1是Asp，Tyr（OH或SE），Ser（OH或SE），Hyp（OH或SE），Thr（OH或SE），Cys，Tyr（OCH3）或desR1; Y是OH或SE; R3是Met，Nva或Nle; R4是Gly，D-Cys或D-Ala; R6是Met，Nva或Nle; R7是Asp，Ser（SE），Thr（SE）或Hyp（SE）; R8是Phe或Tyr（OCH3）; Q为低级烷基，氟低级烷基或氢; 条件是当R 3和R 6为Met且R 7为Asp时，R 4为D-Ala。 也可以使用其药学上可接受的盐。

公开(公告)号：US4216141A

公开(公告)日：1980-08-05

申请号：US926491

申请日：1978-07-19

申请人： Jean E. F. Rivier ,  Robert F. Galyean

发明人： Jean E. F. Rivier ,  Robert F. Galyean

IPC分类号： C07K1/00 ,  C07K1/06 ,  C07K1/12 ,  C07C103/52 ,  C07C149/00

CPC分类号： C07K1/12 ,  C07K1/00 ,  C07K1/067 ,  Y10S930/15 ,  Y10S930/16

摘要： Peptides containing a disulfide bond between two cysteine residues are formed by an oxidation process. The oxidation step is accomplished under conditions whereby the sulfhydryl concentration in a reaction mixture is maintained at substantially zero during the reaction. In the process, an aqueous solution of a peptide containing at least one pair of cysteine moities is added incrementally to a buffered solution containing an oxidizing agent. The period between addition of the increments of the peptide solution is sufficient that the reaction to form the disulfide bond occurs substantially instantaneously. The increments are of such size that the sulfhydryl concentration during the reaction remains substantially constant and at a level of substantially zero, equivalent to infinite dilution.

摘要翻译： 通过氧化过程形成含有两个半胱氨酸残基之间的二硫键的肽。 氧化步骤是在反应期间将反应混合物中的巯基浓度维持在基本为零的条件下完成的。 在该方法中，将含有至少一对半胱氨酸的肽的水溶液逐渐加入到含有氧化剂的缓冲溶液中。 添加肽溶液增量之间的时间足以使形成二硫键的反应基本上瞬间发生。 增量具有这样的尺寸，使得反应期间的巯基浓度保持基本上恒定，并且基本上为零，相当于无限稀释。

公开(公告)号：US07141546B1

公开(公告)日：2006-11-28

申请号：US10210889

申请日：2002-07-31

申请人： Jean E. F. Rivier ,  Wylie W. Vale ,  Marilyn H. Perrin ,  Jozsef Gulyas ,  Dean A. Kirby

发明人： Jean E. F. Rivier ,  Wylie W. Vale ,  Marilyn H. Perrin ,  Jozsef Gulyas ,  Dean A. Kirby

IPC分类号： A61K38/16 ,  C07K14/00

CPC分类号： C07K14/4703 ,  A61K38/00 ,  G01N33/74 ,  G01N2500/02

摘要： CRF peptide analogs that bind to CRFR2 with an affinity far greater than they bind to CRFR1. These analogs exhibit CRF antagonist activity, and they can be based upon the native structures of sauvagine, CRF, and urocortin.

摘要翻译： 结合CRFR2的CRF肽类似物的亲和力远远大于它们与CRFR1结合的亲和力。 这些类似物显示CRF拮抗剂活性，它们可以基于sauvagine，CRF和尿皮质素的天然结构。

公开(公告)号：US06326463B1

公开(公告)日：2001-12-04

申请号：US09424889

申请日：1999-11-29

申请人： Jean E. F. Rivier

发明人： Jean E. F. Rivier

IPC分类号： A61K3828

CPC分类号： C07K14/57509 ,  A61K38/00 ,  G01N33/566 ,  G01N33/68 ,  G01N33/74 ,  G01N2333/5751 ,  Y10S930/26

摘要： Novel cyclic CRF agonist peptides have the amino acid sequence: (cyclo 30-33)Ac-Ser-Leu-Asp-Leu-Thr-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Glu-Ala-R32-R33-Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH2 wherein R32 is His, D-His or an equivalent &agr;-amino acid; R33 is Lys or Orn. The N-terminus may be extended by Tyr, D-Tyr or Ile. Lys may be substituted for Arg23, and its side chain connected by a lactam bridge to Glu20 to form a bicyclic peptide. Certain disclosed CRF agonists include: (cyclo 30-33)[Ac-Ser7, D-Phe12, Nle21,38, Glu30, Lys33]r/hCRF(7-41); (cyclo 30-33)[Ac-Ser7, D-Phe12, Nle21,38, Glu30, D-His32, Lys33]r/hCRF(7-41); (bicyclo 20-23, 30-33)[Ac-Ser7, D-Phe12, Nle21,38, Lys23,33, Glu30, D-His32]-r/hCRF(7-41); (cyclo 30-33)[Ac-Ser7, D-Phe12, Nle18,21, Glu30, D-Ala32, Lys33]&agr;-helicale CRF(7-41); and (cyclo 30-33)[Ac-Ser7, D-Phe12, Nle21,38, CML27,40, Glu30, Lys33]r/hCRF(7-41). Labelled agonist such as (cyclo 30-33)[Ac-I125Tyr6, D-Phe12, Nle21,38, Glu30, Lys33]r/hCRF(6-41) and (cyclo 30-33)[Ac-I125D-Tyr6, D-Phe12, Nle21,38, Glu30, D-His32, Lys33]r/hCRF(6-41) are useful in screening for more potent CRF agonists.

摘要翻译： 新型循环CRF激动剂肽具有氨基酸序列：（环30-33）Ac-Ser-Leu-Asp-Leu-Thr-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle -Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Glu-Ala-R32-R33-Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH2，其中R32是His，D-His 或等效的α-氨基酸; R33是Lys或Orn。 N末端可以被Tyr，D-Tyr或Ile延伸。 Lys可以代替Arg23，其侧链通过内酰胺桥连接至Glu20以形成双环肽。 某些公开的CRF激动剂包括：（环30-33）[Ac-Ser7，D-Phe12，Nle21,38，Glu30，Lys33] r / hCRF（7-41）; （环30-33）[Ac-Ser7，D-Phe12，Nle21,38，Glu30，D-His32，Lys33] r / hCRF（7-41）; （双环20-23,30-33）[Ac-Ser7，D-Phe12，Nle21,38，Lys23,33，Glu30，D-His32] -r / hCRF（7-41）; （环30-33）[Ac-Ser7，D-Phe12，Nle18,21，Glu30，D-Ala32，Lys33]α-螺旋CRF（7-41）; 和（环30-33）[Ac-Ser7，D-Phe12，Nle21,38，CML27,40，Glu30，Lys33] r / hCRF（7-41）。 标记的激动剂如（环30-33）[Ac-I125Tyr6，D-Phe12，Nle21,38，Glu30，Lys33] r / hCRF（6-41）和（环30-33）[Ac-I125D-Tyr6，D -Phe12，Nle21,38，Glu30，D-His32，Lys33] r / hCRF（6-41）可用于筛选更有效的CRF激动剂。

公开(公告)号：US06323312B1

公开(公告)日：2001-11-27

申请号：US09424127

申请日：1999-11-17

申请人： Jean E. F. Rivier

发明人： Jean E. F. Rivier

IPC分类号： A61K3812

CPC分类号： G01N33/74 ,  A61K38/00 ,  C07K14/57509 ,  G01N33/566 ,  G01N2333/5751

摘要： Novel cyclic CRF antagonist peptides are created by shortening the N-terminus of a CRF family peptide by 8 residues and adding an acyl group. CML is present in what would be the 27-position of the native CRF sequence, and a cyclizing bond is created between the side chains of the residues in positions 30 and 33. The side chain of Lys, preferably, in position 33 is linked to the side chain of Glu in position 30 by a lactam bridce. Disclosed CRF antagonists include: (cyclo 30-33)[Ac-Asp9, D-Phe12, Nle21,38, CML27,40, Glu30, Lys33]r/hCRF(9-4); (cyclo 30-33)[Ac-Asp9, D-Phe12, CML18,27, Nle21,38, Glu30, Lys33]r-hCRF(9-41); (cyclo 30-33)[Ac-Asp9, D-Phe12, Nle21,38, CML27,37, Glu30, Lys33]r/hCRF(9-41); (cyclo 30-33)[Ac-Asp9, D-Phe12, CML14,27, Nle21,38, Glu30, Lys33]r/hCRF(9-41); (cyclo 30-33)[Ac-Asp9, D-Phe12, Nle21,38, CML27, Glu30, Lys33]r/hCRF(9-41); and (cyclo 30-33)[Ac-Asp9, D-Phe12, Nle21,38, CML27,40, Glu30, Aib32, Lys33]r/hCRF(9-41).

摘要翻译： 通过将CRF家族肽的N末端缩短8个残基并加入酰基来产生新的循环CRF拮抗剂肽。 CML存在于天然CRF序列的27位上，并且在位置30和33的残基的侧链之间产生环化键。Lys的侧链优选位于33位与 位置30处的Glu的侧链通过内酰胺桥接。 公开的CRF拮抗剂包括：（环30-33）[Ac-Asp9，D-Phe12，Nle21,38，CML27,40，Glu30，Lys33] r / hCRF（9-4）; （环30-33）[Ac-Asp9，D-Phe12，CML18,27，Nle21,38，Glu30，Lys33] r-hCRF（9-41）; （环30-33）[Ac-Asp9，D-Phe12，Nle21,38，CML27,37，Glu30，Lys33] r / hCRF（9-41）; （环30-33）[Ac-Asp9，D-Phe12，CML14,27，Nle21,38，Glu30，Lys33] r / hCRF（9-41）; （环30-33）[Ac-Asp9，D-Phe12，Nle21,38，CML27，Glu30，Lys33] r / hCRF（9-41）; 和（环30-33）[Ac-Asp9，D-Phe12，Nle21,38，CML27,40，Glu30，Aib32，Lys33] r / hCRF（9-41）。

公开(公告)号：US5807986A

公开(公告)日：1998-09-15

申请号：US579216

申请日：1995-12-28

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 termed "betides" mimic peptides and 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 betidamino 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 betidamino acid residue having the formula: ##STR1## wherein R.sub.0 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 or isothiocyanate group, a sulfonyl group or the like. To make a betide, an aminoglycine residue is subjected to side chain acylation, and optionally also alkylation, after it is coupled into a peptide intermediate. By synthesizing betides with multiple substituents at one or more positions in an otherwise peptidic chain, efficient screening of betides which mimic peptides having a large number of different natural or unnatural amino acid substituents at a particular position, and optionally both D- and L-isomers thereof, is possible.

摘要翻译： 称为“betide”的化合物模拟肽并含有一个或多个氨基糖基，Cα-氨基丙氨酸，氨基肌氨酸等残基，其中侧链氨基已被酰化并任选也被烷基化。 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各自独立地为二氨基酸或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R 0是H或CH 3，R 2和R 2是H或低级烷基，R 3是酰基，异氰酸酯或异硫氰酸酯基 ，磺酰基等。 为了使之发生反应，氨基糖残基在其被偶联到肽中间体后进行侧链酰化，并且任选地也进行烷基化。 通过在另一个肽链的一个或多个位置合成具有多个取代基的肽，有效筛选模拟在特定位置具有大量不同天然或非天然氨基酸取代基的肽，以及任选的D-和L-异构体 是可能的。

公开(公告)号：US5777073A

公开(公告)日：1998-07-07

申请号：US865773

申请日：1997-05-30

申请人： Jean E. F. Rivier

发明人： Jean E. F. Rivier

IPC分类号： A61K38/00 ,  A61P1/00 ,  A61P25/00 ,  C07K14/575 ,  G01N33/15 ,  G01N33/50 ,  G01N33/566 ,  G01N33/74 ,  A61K38/28 ,  A61K38/35 ,  C07K5/00 ,  C07K7/00

CPC分类号： G01N33/566 ,  C07K14/57509 ,  G01N33/74 ,  A61K38/00 ,  G01N2333/5751 ,  Y10S930/26 ,  Y10S930/27

摘要： Novel cyclic CRF antagonist peptides are created by shortening the N-terminus of a CRF family peptide by 8-11 residues and adding an acyl group. CML is preferably present in what would be the 27-position of the native CRF sequence, and D-Tyr may be incorporated at the N-terminus to facilitate labelling. The cyclizing bond is preferably created between the side chains of the residues in positions 30 and 33; but it may alternatively be created between the residues in either of positions 28 and 29 with those in positions 31 and 32 or with those in positions 32 and 33, respectively. The side chain of Lys in position 33 is preferably linked to the side chain of Glu in position 30 by a lactam bridge to form the cyclic peptide. Disclosed CRF antagonists include: (cyclo 30-33) �Ac-Asp.sup.9, D-Phe.sup.12, Nle.sup.21,38, CML.sup.27,40, Glu.sup.30, Lys.sup.33 !r/hCRF(9-41), (cyclo 30-33) �Ac-Asp.sup.9, D-Phe.sup.12, Nle.sup.21,38, CML.sup.27,37, Glu.sup.30, Lys.sup.33 !r/hCRF(9-41), (cyclo 30-33) �Ac-Asp.sup.9, D-Phe.sup.12, CML.sup.14,27, Nle.sup.21,38, Glu.sup.30, Lys.sup.33 !r/hCRF(9-41), (cyclo 30-33) �Ac-Asp.sup.9, D-Phe.sup.12, Nle.sup.21,38, CML.sup.27, Glu.sup.30, Lys.sup.33 !r/hCRF(9-41), (cyclo 30-33) �Ac-Asp.sup.9, D-Phe.sup.12, CML.sup.18,27, Nle.sup.21,38, Glu.sup.30, D-His.sup.32, Lys.sup.33 !r/hCRF(9-41) and (cyclo 30-33) �Ac-Asp.sup.9, D-Phe.sup.12, CML.sup.18,27, Nle.sup.21,38, Glu.sup.30, Lys.sup.33 !r/hCRF(9-41).

摘要翻译： 通过将CRF家族肽的N末端缩短8-11个残基并加入酰基来产生新的循环CRF拮抗剂肽。 CML优选存在于天然CRF序列的27位上，并且D-Tyr可以并入N末端以促进标记。 优选在位置30和33之间的残基的侧链之间产生环化键; 但也可以分别在位置28和29之间的残基与位置31和32中的残基之间或位于第32和33位的残基之间产生。 位置33处的Lys侧链优选通过内酰胺桥连接于位置30的Glu侧链以形成环肽。 公开的CRF拮抗剂包括：（环30-33）[Ac-Asp9，D-Phe12，Nle21,38，CML27,40，Glu30，Lys33] r / hCRF（9-41），（环30-33）[Ac- Asp9，D-Phe12，Nle21,38，CML27,37，Glu30，Lys33] r / hCRF（9-41），（环30-33）[Ac-Asp9，D-Phe12，CML14,27，Nle21,38， Glu30，Lys33] r / hCRF（9-41），（环30-33）[Ac-Asp9，D-Phe12，Nle21,38，CML27，Glu30，Lys33] r / hCRF（9-41），（环30 -33）[Ac-Asp9，D-Phe12，CML18,27，Nle21,38，Glu30，D-His32，Lys33] r / hCRF（9-41）和（环30-33）[Ac-Asp9， Phe12，CML18,27，Nle21,38，Glu30，Lys33] r / hCRF（9-41）。

公开(公告)号：US5371070A

公开(公告)日：1994-12-06

申请号：US973989

申请日：1992-11-09

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

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

IPC分类号： A61K38/00 ,  C07K7/02 ,  C07K7/23 ,  C07K7/06 ,  A61K37/38 ,  C07K5/12

CPC分类号： C07K7/02 ,  C07K7/23 ,  A61K38/00

摘要： Peptides which have substantial bioactivity to inhibit the secretion of gonadotropins by the pituitary gland and to inhibit the release of steroids by the gonads. Administration of an effective amount of such GnRH antagonists prevents ovulation and/or the release of steroids by the gonads. They may also be used to treat steroid-dependent tumors, such as prostatic and mammary tumors. The peptides are bicyclic analogs of the decapeptide GnRH having two covalent bonds, between the residues in the 4- and 10-positions and the residues in the 5- and 8-positions. The latter linkage includes peptide bonds between a residue of an .alpha.-amino acid outside of the main chain and a side-chain carboxyl group of the 5-position residue and a side-chain amino group of the 8-position residue.

摘要翻译： 具有大量生物活性以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拮抗剂可防止性腺的排卵和/或释放类固醇。 它们也可用于治疗类固醇依赖性肿瘤，如前列腺和乳腺肿瘤。 肽是具有两个共价键的十肽GnRH的双环类似物，在4-和10-位之间的残基和5-和8-位的残基之间。 后一连接包括在主链外部的α-氨基酸的残基与5位残基的侧链羧基和8位残基的侧链氨基之间的肽键。

公开(公告)号：US5169935A

公开(公告)日：1992-12-08

申请号：US541810

申请日：1990-06-20

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

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

IPC分类号： C07K1/06 ,  C07K7/23

CPC分类号： C07K1/064 ,  C07K7/23 ,  Y02P20/55

摘要： Methods for making peptides of a suitable length for solid phase synthesis, which peptides include in their sequence a pair of residues of a different character which have acylated side chains and a residue which has an N-alkylated side chain. A peptide intermediate is constructed on the resin using commercially available starting materials. The N-terminus can be acylated by removing the .alpha.-amino protecting group and acylating under standard conditions. First primary amino protecting groups included in those residues to be acylated are removed, and acylation is effected, preferably by using a carboxypyridine or a similar heterocyclic acylating agent. Following such side chain acylation, a second protecting group included in the residue to be N-alkylated is removed, and the N-alkylation reaction is carried out while the peptide remains on the resin using a borohydride and an appropriate aldehyde or ketone. Following cleavage from the resin and removal of any protecting groups still remaining, the peptide is appropriately purified, thus requiring only a single purification to be carried out while forming a synthetic peptide including residues for which the modified amino acids are not readily commercially available.

摘要翻译： 制备用于固相合成的合适长度的肽的方法，该肽在其序列中包括具有酰化侧链的不同特征的残基和具有N-烷基化侧链的残基。 使用市售原料在树脂上构建肽中间体。 可以通过除去α-氨基保护基并在标准条件下酰化来酰化N-末端。 除去要被酰化残留物中包括的第一个伯氨基保护基，优选通过使用羧基吡啶或类似的杂环酰化剂进行酰化。 在这样的侧链酰化之后，除去待N-烷基化的残基中的第二保护基，并且使用硼氢化钠和适当的醛或酮在肽保留在树脂上的同时进行N-烷基化反应。 在从树脂切割并除去仍然保留的任何保护基之后，肽被适当地纯化，因此仅需要进行单次纯化，同时形成包含修饰氨基酸不容易商业获得的残基的合成肽。

公开(公告)号：US4701499A

公开(公告)日：1987-10-20

申请号：US799339

申请日：1986-02-03

申请人： Wayne D. Kornreich ,  Harry A. Anderson ,  John S. Porter ,  Jean E. F. Rivier

发明人： Wayne D. Kornreich ,  Harry A. Anderson ,  John S. Porter ,  Jean E. F. Rivier

IPC分类号： C07K1/04 ,  C07K5/097 ,  C08F8/18 ,  C08F12/08 ,  C08F112/08 ,  C08F212/08

CPC分类号： C07K5/0823 ,  C07K1/04 ,  Y10S930/28

摘要： Peptide N-alkylamides, and other C-terminal N-substituted amides, can be synthesized using solid-phase synthesis on a benzene-containing resin which is suitably methylated. Reactive amino groups are attached directly or indirectly to the methyl groups, for example, such as by reacting commercially available chloromethylated polystyrene resins with an alkylamine to create a resin-amine. The C-terminal amino acid of the desired peptide is linked to the resin-amine via an amide linkage, and the peptide is thereafter built in normal fashion. Treatment of the completed peptide intermediate with HF is effective to both effect deprotection and cleave the peptide from the resin in the form of the N-substituted amide. Examples include peptide N-ethylamides, N-fluoroethylamide, N-anilides and other substituted N-benzylamides.

摘要翻译： 肽N-烷基酰胺和其它C-末端N-取代的酰胺可以使用合适甲基化的含苯树脂上的固相合成来合成。 反应性氨基直接或间接连接到甲基上，例如通过使市售氯甲基化聚苯乙烯树脂与烷基胺反应以产生树脂 - 胺。 所需肽的C-末端氨基酸通过酰胺键与树脂 - 胺连接，然后以正常方式构建肽。 用HF处理完成的肽中间体可有效地进行脱保护并以N-取代酰胺的形式从树脂切割肽。 实例包括肽N-乙酰胺，N-氟乙基酰胺，N-酰苯胺和其它取代的N-苄基酰胺。