公开(公告)号：US06515103B1

公开(公告)日：2003-02-04

申请号：US09142080

申请日：2000-05-11

Applicant: Fe C. Abogadie ,  Lourdes J. Cruz ,  Baldomero M. Olivera ,  Craig Walker ,  Clark Colledge ,  David R. Hillyard ,  Elsie Jimenez ,  Richard T. Layer ,  Li-Ming Zhou ,  Gregory S. Shen ,  R. Tyler McCabe ,  Jean E. Rivier

Inventor： Fe C. Abogadie ,  Lourdes J. Cruz ,  Baldomero M. Olivera ,  Craig Walker ,  Clark Colledge ,  David R. Hillyard ,  Elsie Jimenez ,  Richard T. Layer ,  Li-Ming Zhou ,  Gregory S. Shen ,  R. Tyler McCabe ,  Jean E. Rivier

IPC: A61K3800

CPC classification number: C07K14/43504 ,  A61K38/00

Abstract: The present invention is directed to conantokin peptides, conantokin peptide derivatives and conantokin peptide chimeras, referred to collectively as conantokins, having 10-30 amino acids, including preferably two or more &ggr;-carboxyglutamic acid residues. The conantokins are useful for the treatment of neurologic and psychiatric disorders, such as anticonvulsant agents, neuroprotective agents or analgesic agents.

Abstract translation: 本发明涉及具有10-30个氨基酸，包括优选两个或更多个γ-羧基谷氨酸残基的组合蛋白肽，柯南多肽衍生物和柯南鸟肽嵌合体，统称为聚对二聚体。 凝血因子可用于治疗神经和精神疾病，例如抗惊厥剂，神经保护剂或止痛剂。

公开(公告)号：US6077934A

公开(公告)日：2000-06-20

申请号：US61026

申请日：1998-04-16

Applicant: Richard Jacobsen ,  Elsie Jimenez ,  Lourdes J. Cruz ,  Baldomero M. Olivera ,  William R. Gray ,  Michelle Grilley ,  Maren Watkins ,  David R. Hillyard

Inventor： Richard Jacobsen ,  Elsie Jimenez ,  Lourdes J. Cruz ,  Baldomero M. Olivera ,  William R. Gray ,  Michelle Grilley ,  Maren Watkins ,  David R. Hillyard

IPC: A61K38/00 ,  C07K7/06 ,  C07K5/00

CPC classification number: C07K7/06 ,  A61K38/00 ,  Y10S530/857

Abstract: The present invention is directed to contryphan peptides having 6-12 amino acids, preferably including one or more D-tryptophan or D-leucine residues. The peptides of the present invention are generically termed "contryphans," although the D-leucine containing contryphans are sometimes referred to as leu-contryphans. More specifically, the present invention is directed to contryphan peptides having the general formula Xaa.sub.1 -Cys-Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.4 -Pro-Xaa.sub.5 -Cys (SEQ ID NO:1), wherein Xaa.sub.1, is any amino acid or des-Xaa.sub.1, Xaa.sub.2 is Pro, 4-trans-hydroxyproline or Val, Xaa.sub.3 is D-Trp, L-Trp, D-Leu or L-Leu, preferably D-Trp or D-Leu, Xaa.sub.4 is any amino acid and Xaa.sub.5 is Trp or Tyr. When the peptide contains Xaa.sub.1, it is preferably Gly, Glu, or Lys, most preferably Gly. When Xaa.sub.3 is D- or L-Trp, Xaa.sub.2 is preferably Pro or 4-trans-hydroxyproline. When Xaa.sub.3 is D- or L-Leu, Xaa.sub.2 is preferably Val. The carboxy terminus may contain a carboxyl or an amide, preferably an amide. The present invention is further directed to the specific contryphan peptides and propeptides as described herein. The present invention is also directed to nucleic acids encoding the contryphan peptides and their propeptides as described herein. The contryphans of the present invention are useful as anticonvulsant or neuroprotective agents.

Abstract translation: 本发明涉及具有6-12个氨基酸的优选肽，优选包括一个或多个D-色氨酸或D-亮氨酸残基。 本发明的肽通常被称为“contryphans”，尽管含有D-亮氨酸的对应物有时被称为leu-contryphans。 更具体地，本发明涉及具有通式Xaa1-Cys-Xaa2-Xaa3-Xaa4-Pro-Xaa5-Cys（SEQ ID NO：1）的反式肽，其中Xaa1是任何氨基酸或des-Xaa1， Xaa2是Pro，4-反 - 羟脯氨酸或Val，Xaa3是D-Trp，L-Trp，D-Leu或L-Leu，优选D-Trp或D-Leu，Xaa4是任何氨基酸，Xaa5是Trp或Tyr 。 当肽含有Xaa1时，其优选为Gly，Glu或Lys，最优选为Gly。 当Xaa3为D-或L-Trp时，Xaa2优选为Pro或4-反式 - 羟脯氨酸。 当Xaa3为D-或L-Leu时，Xaa2优选为Val。 羧基末端可以含有羧基或酰胺，优选酰胺。 本发明进一步针对如本文所述的特异性抗原肽和前肽。 本发明还涉及编码本文所述的敌百虫肽及其前肽的核酸。 本发明的对策可用作抗惊厥药或神经保护剂。

公开(公告)号：US20050096270A1

公开(公告)日：2005-05-05

申请号：US10894314

申请日：2004-07-20

Applicant: Craig Walker ,  Reshma Shetty ,  Elsie Jimenez ,  J. McIntosh ,  Baldomero Olivera ,  Maren Watkins ,  Robert Jones ,  Gregory Shen

Inventor： Craig Walker ,  Reshma Shetty ,  Elsie Jimenez ,  J. McIntosh ,  Baldomero Olivera ,  Maren Watkins ,  Robert Jones ,  Gregory Shen

IPC: C07K14/435 ,  A61K38/16

CPC classification number: C07K14/43504

Abstract: The invention relates to relatively short peptides (termed 1-conotoxins herein), about 30-50 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include four disulfide bonds.

Abstract translation: 本发明涉及相对短的肽（本文中称为1-芋螺毒素），长度约30-50个残基，其在锥形蜗牛的毒液中天然可以微量天然存在或类似于天然可得的肽，并且优选包括四个 二硫键。

公开(公告)号：US5889147A

公开(公告)日：1999-03-30

申请号：US785534

申请日：1997-01-17

Applicant: Lourdes J. Cruz ,  Baldomero M. Olivera ,  J. Michael McIntosh ,  Elsie Jimenez ,  A. Grey Craig ,  Jean A. Rivier ,  David Julius ,  Laura England

Inventor： Lourdes J. Cruz ,  Baldomero M. Olivera ,  J. Michael McIntosh ,  Elsie Jimenez ,  A. Grey Craig ,  Jean A. Rivier ,  David Julius ,  Laura England

IPC: A61K38/00 ,  C07K5/10 ,  C07K5/117 ,  C07K7/06 ,  C07K14/435 ,  A61K38/08 ,  A61K38/10 ,  A61K38/16 ,  C07K7/04

CPC classification number: C07K7/06 ,  C07K14/43504 ,  C07K5/1024 ,  C07K5/1027 ,  A61K38/00

Abstract: The present invention is directed to conopeptides having 6-45 amino acids, including one or more bromo-tryptophan residues. More specifically, the present invention is directed to conopeptides having the general formula: R-(Cys).sub.n -R.sup.1 -B-R.sup.2 -Cys-R.sup.3, wherein R is a peptide chain of 0-24 amino acids, R.sup.1 is a peptide chain of 0 to 31 amino acids, R.sup.2 is a peptide chain of 0-29 amino acids, R.sup.3 is a peptide chain of 0 to 26 amino acids, B is 6-bromo-tryptophan, n is 0 or 1 and the total length of the conopeptide is from about 6 to about 45 amino acids. The invention also includes pharmaceutically acceptable salts of the conopeptides. These bromo-tryptophan containing conopeptides invention are useful as antihelminthic agents, anti-vomiting agents, sleep-inducing agents, adjuncts to anesthesia, anticonvulsant or neuroprotective agents.

Abstract translation: 本发明涉及具有6-45个氨基酸的肽，包括一个或多个溴 - 色氨酸残基。 更具体地，本发明涉及具有以下通式的肽：R-（Cys）n -R 1 -B-R 2 -Cys-R 3，其中R是0-24个氨基酸的肽链，R 1是肽链 0至31个氨基酸，R2为0-29个氨基酸的肽链，R3为0至26个氨基酸的肽链，B为6-溴色氨酸，n为0或1，总长度为 肽是约6至约45个氨基酸。 本发明还包括肽的药学上可接受的盐。 这些含有溴代色氨酸的多肽本发明可用作抗凝血剂，抗呕吐剂，睡眠诱导剂，麻醉剂，抗惊厥药或神经保护剂。

公开(公告)号：US6153738A

公开(公告)日：2000-11-28

申请号：US466138

申请日：1999-12-21

Applicant: Richard Jacobsen ,  Elsie Jimenez ,  Lourdes J. Cruz ,  Baldomero M. Olivera ,  William R. Gray ,  Michelle Grilley ,  Maren Watkins ,  David R. Hillyard

Inventor： Richard Jacobsen ,  Elsie Jimenez ,  Lourdes J. Cruz ,  Baldomero M. Olivera ,  William R. Gray ,  Michelle Grilley ,  Maren Watkins ,  David R. Hillyard

IPC: A61K38/00 ,  C07K7/06 ,  C07H21/04

CPC classification number: C07K7/06 ,  A61K38/00 ,  Y10S530/857

Abstract: The present invention is directed to contryphan peptides having 6-12 amino acids, preferably including one or more D-tryptophan or D-leucine residues. The peptides of the present invention are generically termed "contryphans," although the D-leucine containing contryphans are sometimes referred to as leu-contryphans. More specifically, the present invention is directed to contryphan peptides having the general formula Xaa.sub.1 -Cys-Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.4 -Pro-Xaa.sub.5 -Cys (SEQ ID NO:1), wherein Xaa.sub.1 is any amino acid or des-Xaa.sub.1, Xaa.sub.2 is Pro, 4-trans-hydroxyproline or Val, Xaa.sub.3 is D-Trp, L-Trp, D-Leu or L-Leu, preferably D-Trp or D-Leu, Xaa.sub.4 is any amino acid and Xaa.sub.5 is Trp or Tyr. When the peptide contains Xaa.sub.1, it is preferably Gly, Glu, or Lys, most preferably Gly. When Xaa.sub.3 is D- or L-Trp, Xaa.sub.2 is preferably Pro or 4-trans-hydroxyproline. When Xaa.sub.3 is D- or L-Leu, Xaa.sub.2 is preferably Val. The carboxy terminus may contain a carboxyl or an amide, preferably an amide. The present invention is further directed to the specific contryphan peptides and propeptides as described herein. The present invention is also directed to nucleic acids encoding the contryphan peptides and their propeptides as described herein. The contryphans of the present invention are useful as anticonvulsant or neuroprotective agents.

Abstract translation: 本发明涉及具有6-12个氨基酸的优选肽，优选包括一个或多个D-色氨酸或D-亮氨酸残基。 本发明的肽通常被称为“contryphans”，尽管含有D-亮氨酸的对应物有时被称为leu-contryphans。 更具体地说，本发明涉及具有通式Xaa1-Cys-Xaa2-Xaa3-Xaa4-Pro-Xaa5-Cys（SEQ ID NO：1）的反式肽，其中Xaa1是任何氨基酸或des-Xaa1，Xaa2 是Pro，4-反式 - 羟基脯氨酸或Val，Xaa3是D-Trp，L-Trp，D-Leu或L-Leu，优选D-Trp或D-Leu，Xaa4是任何氨基酸，Xaa5是Trp或Tyr。 当肽含有Xaa1时，其优选为Gly，Glu或Lys，最优选为Gly。 当Xaa3为D-或L-Trp时，Xaa2优选为Pro或4-反式 - 羟脯氨酸。 当Xaa3为D-或L-Leu时，Xaa2优选为Val。 羧基末端可以含有羧基或酰胺，优选酰胺。 本发明进一步针对如本文所述的特异性抗原肽和前肽。 本发明还涉及编码本文所述的敌百虫肽及其前肽的核酸。 本发明的对策可用作抗惊厥药或神经保护剂。