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    Gamma-conopeptides
    25.
    发明授权
    Gamma-conopeptides 有权
    伽玛肽

    公开(公告)号：US06624288B1

    公开(公告)日：2003-09-23

    申请号：US09210952

    申请日：1998-12-15

    申请人： Michael Fainzilber ,  Karel S. Kits ,  Alma L. Burlingame ,  Baldomero M. Olivera ,  Craig Walker ,  Maren Watkins ,  Reshma Shetty ,  Lourdes J. Cruz ,  Julita Imperial ,  Clark Colledge

    发明人： Michael Fainzilber ,  Karel S. Kits ,  Alma L. Burlingame ,  Baldomero M. Olivera ,  Craig Walker ,  Maren Watkins ,  Reshma Shetty ,  Lourdes J. Cruz ,  Julita Imperial ,  Clark Colledge

    IPC分类号： C07K500

    CPC分类号： C07K14/43504 ,  A61K38/00

    摘要： This invention relates to relatively short peptides about 25-40 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogs to the naturally available peptides, and which include three cyclizing disulfide linkages and one or more &ggr;-carboxyglutamate residues. More specifically, the present invention is directed to &ggr;-conopeptides having the general formula I: Xaa1-Cys-Xaa2-Cys-Xaa3-Xaa4-Cys-Cys-Xaa5-Cys-Xaa6-Cys-Xaa7 (SEQ ID NO:1), as described herein; or having the general formula II: Xaa1-Cys-Xaa2-Cys-Xaa3-Xaa4-Cys-Cys-Xaa5-Xaa6-Cys-Xaa7-Cys-Xaa8 (SEQ ID NO:2), as defined herein; or having the general formula III: Xaa1-Cys-Xaa2-Cys-Xaa3-Xaa4-Xaa5-Cys-Cys-Ser-Asn-Ser-Cys-Asp-Xaa2-Cys-Xaa7 (SEQ ID NO:3), as described herein; or having the general formula IV: Xaa1-Cys-Xaa2-Cys-Xaa3-Xaa4-Xaa5-Cys-Cys-Ser-Asn-Ser-Cys-Asp-Xaa6-Cys-Xaa7 (SEQ ID NO:4), as described herein; or having the general formula V: Xaa1-Xaa2-Cys-Xaa3-Xaa4-Phe-Xaa5-Cys-Thr-Xaa6-Ser-Xaa7-Cys-Cys-Ser-Asn-Ser-Cys-Asp-Gln-Thr-Tyr-Cys-Xaa8-Leu-Xaa9 (SEQ ID NO:5), as described herein. The invention further relates to specific &ggr;-conopeptides, specific pro-&ggr;-conopeptides and nucleic acids encoding the pro-&ggr;-conopeptides. The invention also includes pharmaceutically acceptable salts of the conopeptides. These conopeptides are useful as agonists of neuronal pacemaker calcium channels.

    摘要翻译： 本发明涉及长度约25-40个残基的相对较短的肽，其在锥形蜗牛的毒液中或天然存在的肽的类似物中天然可用量少，并且其包括三个环化二硫键和一个或多个γ- 羧基谷氨酸残基。 更具体地，本发明涉及具有通式I的X射线衍生肽：Xaa1-Cys-Xaa2-Cys-Xaa3-Xaa4-Cys-Cys-Xaa5-Cys-Xaa6-Cys-Xaa7（SEQ ID NO：1） ，如本文所述; 或具有如本文所定义的通式II：Xaa1-Cys-Xaa2-Cys-Xaa3-Xaa4-Cys-Cys-Xaa5-Xaa6-Cys-Xaa7-Cys-Xaa8（SEQ ID NO：2） 或具有通式III：Xaa1-Cys-Xaa2-Cys-Xaa3-Xaa4-Xaa5-Cys-Cys-Ser-Asn-Ser-Cys-Asp-Xaa2-Cys-Xaa7（SEQ ID NO：3） 在这里 或具有通式IV：Xaa1-Cys-Xaa2-Cys-Xaa3-Xaa4-Xaa5-Cys-Cys-Ser-Asn-Ser-Cys-Asp-Xaa6-Cys-Xaa7（SEQ ID NO：4） 在这里 或具有通式V：Xaa1-Xaa2-Cys-Xaa3-Xaa4-Phe-Xaa5-Cys-Thr-Xaa6-Ser-Xaa7-Cys-Cys-Ser-Asn-Ser-Cys-Asp-Gln-Thr-Tyr -Cys-Xaa8-Leu-Xaa9（SEQ ID NO：5），如本文所述。 本发明进一步涉及具体的γ-配体肽，特异性前-γ-肽和编码前γ-多肽的核酸。 本发明还包括肽的药学上可接受的盐。 这些肽可用作神经元起搏器钙通道的激动剂。

    Contryphan peptides
    26.
    发明授权
    Contryphan peptides 有权
    对角han肽

    公开(公告)号：US6153738A

    公开(公告)日：2000-11-28

    申请号：US466138

    申请日：1999-12-21

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

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

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

    CPC分类号： C07K7/06 ,  A61K38/00 ,  Y10S530/857

    摘要： 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.

    摘要翻译： 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。

    Contryphan peptides
    29.
    发明授权
    Contryphan peptides 失效
    对角han肽

    公开(公告)号：US6077934A

    公开(公告)日：2000-06-20

    申请号：US61026

    申请日：1998-04-16

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

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

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

    CPC分类号： C07K7/06 ,  A61K38/00 ,  Y10S530/857

    摘要： 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.

    摘要翻译： 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。

    Conotoxin peptide PIIIA
    30.
    发明授权
    Conotoxin peptide PIIIA 失效
    芋螺毒肽PIIIA

    公开(公告)号：US5670622A

    公开(公告)日：1997-09-23

    申请号：US599556

    申请日：1996-02-15

    申请人： Ki-Joon Shon ,  Doju Yoshikami ,  Maren Marsh ,  Lourdes J. Cruz ,  David R. Hillyard ,  Baldomero M. Olivera

    发明人： Ki-Joon Shon ,  Doju Yoshikami ,  Maren Marsh ,  Lourdes J. Cruz ,  David R. Hillyard ,  Baldomero M. Olivera

    IPC分类号： A61K38/00 ,  C07K14/435 ,  C07K14/00

    CPC分类号： C07K14/435 ,  A61K38/00 ,  Y10S530/855

    摘要： The invention is directed to a new .mu.-conotoxin named GIIIA. .mu.-Conotoxin PIIIA consists of 22 amino residues and is found in the Eastern Pacific fish-hunting species Conus purpurascens. This conotoxin is a new Na.sup.+ channel blocker and can be used to resolve tetrodotoxin-sensitive sodium channels into three categories: 1) sensitive to .mu.-PIIIA and .mu.-conotoxin GIIIA; 2) sensitive to .mu.-PIIIA but not to .mu.-GIIIA; and 3) sensitive to neither of these two .mu.-conotoxins. In rat brain, binding competition studies between the two .mu.-conotoxins and saxitoxin suggest at least three pharmacologically distinguishable binding sites. Thus, .mu.-conotoxin PIIIA should be a key tool for distinguishing among different sodium channel subtypes.

    摘要翻译： 本发明涉及一种名为GIIIA的新型mu -conotoxin。 mu-毒素PIIIA由22个氨基酸残基组成，在东太平洋狩猎物种Conus purpurascens中发现。 这种芋螺毒素是一种新的Na +通道阻断剂，可用于将河豚毒素敏感的钠通道分解为三类：1）对mu -PIIIA和mu -conotoxin GIIIA敏感; 2）对mu -PIIIA敏感但不对mu-GIIIA敏感; 和3）对这两种mu -conotoxins都不敏感。 在大鼠脑中，两种mu-毒素和saxitoxin之间的结合竞争研究表明至少有三个药理学上可区分的结合位点。 因此，mu -conotoxin PIIIA应该是区分不同钠通道亚型的关键工具。