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    Conotoxin peptides
    1.
    发明授权
    Conotoxin peptides 失效
    芋螺毒素肽

    公开(公告)号：US5595972A

    公开(公告)日：1997-01-21

    申请号：US487174

    申请日：1995-06-07

    申请人： Baldomero M. Olivera ,  Lourdes J. Cruz ,  David R. Hillyard ,  J. Michael McIntosh ,  Ameurfino D. Santos

    发明人： Baldomero M. Olivera ,  Lourdes J. Cruz ,  David R. Hillyard ,  J. Michael McIntosh ,  Ameurfino D. Santos

    IPC分类号： A61K38/00 ,  A61K38/17 ,  A61K39/00 ,  A61K49/00 ,  A61P35/00 ,  C07K14/435 ,  A61K38/10

    CPC分类号： C07K14/435 ,  A61K38/17 ,  C07K14/43504 ,  A61K39/00 ,  Y10S436/813

    摘要： The invention is directed to A-lineage conotoxin peptides, which are conotoxin peptides that have strong homology in the signal sequence and the 3'-untranslated region of the genes coding for these peptides to the sequences in the .alpha.-conotoxin peptides. The A-lineage conotoxin peptides include the .alpha.-conotoxin peptides, the .alpha.-conotoxin-like peptides and the .kappa.-conotoxin peptides, described further below. The .alpha.-conotoxin-peptides generally share a "core" sequence motif. This core sequence is termed the .alpha.3/5 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO: 1). The .alpha.-conotoxin-like peptides generally share a core sequence termed the .alpha.4/7 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO:2). The .kappa.-conotoxin peptides generally have a core sequence termed the .kappa.7/2/1/3 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys-Xaa-Cys-Xaa-Xaa-Xaa-Cys (SEQ ID NO:3) .alpha.-conotoxins MII (SEQ ID NO:54) and U002 (SEQ ID NO:10) preferentially bind to neuronal nicotinic acetylcholine receptors, rather than neuromuscular receptors. These latter two conotoxins can be used to diagnose and treat small-cell lung carcinomas, which have cholinergic nicotinic receptors.

    摘要翻译： 本发明涉及A系血凝素毒素肽，其是在编码这些肽的基因的信号序列和3'非翻译区与α-毒素肽序列中具有强同源性的芋螺毒素肽。 A系血凝素毒素肽包括下文进一步描述的α-毒素肽，α-毒素样肽和κ-毒素肽。 α-毒素 - 肽通常共有“核心”序列基序。 该核心序列称为α3/ 5核，并表示为Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys（SEQ ID NO：1）。 α-类毒素样肽通常共有称为α4/7核心的核心序列，并表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa -Cys（SEQ ID NO：2）。 κ-毒素肽通常具有称为kappa 7/2/1/3核心的核心序列，并且表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys -Xaa-Cys-Xaa-Xaa-Xaa-Cys（SEQ ID NO：3）α-毒素MII（SEQ ID NO：54）和U002（SEQ ID NO：10）优先结合神经元烟碱乙酰胆碱受体，而不是神经肌肉 受体。 后两种芋螺毒素可用于诊断和治疗具有胆碱能烟碱受体的小细胞肺癌。

    Process and primers for identifying nucleic acids encoding A-lineage conotoxin peptides
    2.
    发明授权
    Process and primers for identifying nucleic acids encoding A-lineage conotoxin peptides 失效
    用于鉴定编码A谱系芋螺毒素肽的核酸的方法和引物

    公开(公告)号：US5589340A

    公开(公告)日：1996-12-31

    申请号：US477383

    申请日：1995-06-07

    申请人： Baldomero M. Olivera ,  Lourdes J. Cruz ,  David R. Hillyard ,  J. Michael McIntosh ,  Ameurfino D. Santos

    发明人： Baldomero M. Olivera ,  Lourdes J. Cruz ,  David R. Hillyard ,  J. Michael McIntosh ,  Ameurfino D. Santos

    IPC分类号： A61K38/00 ,  A61K39/00 ,  C07K14/435 ,  C12Q1/68 ,  C07H21/04 ,  C12P19/34

    CPC分类号： C07K14/435 ,  C07K14/43504 ,  A61K38/00 ,  A61K39/00

    摘要： The invention is directed to A-lineage conotoxin peptides, which are conotoxin peptides that have strong homology in the signal sequence and the 3'-untranslated region of the genes coding for these peptides to the sequences in the .alpha.-conotoxin peptides. The A-lineage conotoxin peptides include the .alpha.-conotoxin peptides, the .alpha.-conotoxin-like peptides and the .kappa.-conotoxin peptides, described further below. The .alpha.-conotoxin-peptides generally share a "core" sequence motif. This core sequence is termed the .alpha. 3/5 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO: 1). The .alpha.-conotoxin-like peptides generally share a core sequence termed the .alpha. 4/7 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO: 2). The .kappa.-conotoxin peptides generally have a core sequence termed the .kappa.7/2/1/3 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys-Xaa-Cys-Xaa-Xaa-Xaa-Cys (SEQ ID NO: 3).

    摘要翻译： 本发明涉及A系血凝素毒素肽，其是在编码这些肽的基因的信号序列和3'非翻译区与α-毒素肽序列中具有强同源性的芋螺毒素肽。 A系血凝素毒素肽包括下文进一步描述的α-毒素肽，α-毒素样肽和κ-毒素肽。 α-毒素 - 肽通常共有“核心”序列基序。 该核心序列称为α+ E，fra 3/5 + EE核心，并表示为Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys（SEQ ID NO：1 ）。 α-类毒素样肽通常共有称为α+ E，f 4/7 + EE核心的核心序列，并表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa -Xaa-Xaa-Xaa-Cys（SEQ ID NO：2）。 κ-毒素肽通常具有称为kappa 7/2/1/3核心的核心序列，并且表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys -Xaa-Cys-Xaa-Xaa-Xaa-Cys（SEQ ID NO：3）。

    Conotoxin peptides
    3.
    发明授权
    Conotoxin peptides 失效
    芋螺毒素肽

    公开(公告)号：US5633347A

    公开(公告)日：1997-05-27

    申请号：US480750

    申请日：1995-06-07

    申请人： Baldomero M. Olivera ,  Lourdes J. Cruz ,  David R. Hillyard ,  J. Michael McIntosh ,  Ameurfino O. Santos

    发明人： Baldomero M. Olivera ,  Lourdes J. Cruz ,  David R. Hillyard ,  J. Michael McIntosh ,  Ameurfino O. Santos

    IPC分类号： A61K38/00 ,  A61K39/00 ,  C07K14/435

    CPC分类号： C07K14/435 ,  C07K14/43504 ,  A61K38/00 ,  A61K39/00 ,  Y10S530/857

    摘要： The invention is directed to A-lineage conotoxin peptides, which are conotoxin peptides that have strong homology in the signal sequence and the 3'-untranslated region of the genes coding for these peptides to the sequences in the .alpha.-conotoxin peptides. The A-lineage conotoxin peptides include the .alpha.-conotoxin peptides, the .alpha.-conotoxin-like peptides and the .kappa.-conotoxin peptides, described further below. The .alpha.-conotoxin-peptides generally share a "core" sequence motif. This core sequence is termed the .alpha.3/5 core and is represented as Cys-Cys-Xaa-Xaa-Xaa- Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO:1). The .alpha.-conotoxin-like peptides generally share a core sequence termed the .alpha.4/7 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa- Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO:2). The .kappa.-conotoxin peptides generally have a core sequence termed the .kappa.7/2/1/3 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa- Xaa-Cys-Xaa-Xaa-Cys-Xaa-Cys-Xaa-Xaa-Xaa-Cys (SEQ ID NO:3).

    摘要翻译： 本发明涉及A系血凝素毒素肽，其是在编码这些肽的基因的信号序列和3'非翻译区与α-毒素肽序列中具有强同源性的芋螺毒素肽。 A系血凝素毒素肽包括下文进一步描述的α-毒素肽，α-毒素样肽和κ-毒素肽。 α-毒素 - 肽通常共有“核心”序列基序。 该核心序列称为α3/5核心，并表示为Cys-Cys-Xaa-Xaa-Xaa- Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys（SEQ ID NO：1）。 α-类毒素样肽通常共有称为α4/7核心的核心序列，并表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa- Xaa-Xaa-Xaa-Xaa-Xaa-Xaa -Cys（SEQ ID NO：2）。 κ-毒素肽通常具有称为κ7/2/1/3核心的核心序列，并且表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa- Xaa-Cys-Xaa-Xaa-Cys -Xaa-Cys-Xaa-Xaa-Xaa-Cys（SEQ ID NO：3）。

    Conotoxin peptides
    4.
    发明授权
    Conotoxin peptides 失效
    芋螺毒素肽

    公开(公告)号：US5514774A

    公开(公告)日：1996-05-07

    申请号：US137800

    申请日：1993-10-19

    申请人： Baldomero M. Olivera ,  Lourdes J. Cruz ,  David R. Hillyard ,  J. Michael McIntosh ,  Ameurfina D. Santos

    发明人： Baldomero M. Olivera ,  Lourdes J. Cruz ,  David R. Hillyard ,  J. Michael McIntosh ,  Ameurfina D. Santos

    IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K39/00 ,  C07K7/06 ,  C07K7/08 ,  C07K14/435 ,  C12N15/12 ,  C07K7/00 ,  A61K38/04

    CPC分类号： C07K14/43504 ,  C07K14/435 ,  A61K38/00 ,  A61K39/00

    摘要： The invention is directed to A-lineage conotoxin peptides, which are conotoxin peptides that have strong homology in the signal sequence and the 3'-untranslated region of the genes coding for these peptides to the sequences in the .alpha.-conotoxin peptides. The A-lineage conotoxin peptides include the .alpha.-conotoxin peptides, the .alpha.-conotoxin-like peptides and the .kappa.-conotoxin peptides, described further below. The .alpha.-conotoxin-peptides generally share a "core" sequence motif. This core sequence is termed the .alpha.3/5 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO:1). The .alpha.-conotoxin-like peptides generally share a core sequence termed the .alpha.4/7 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO:2). The .kappa.-conotoxin peptides generally have a core sequence termed the .kappa.7/2/1/3 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys-Xaa-Cys-Xaa-Xaa-Xaa-Cys (SEQ ID NO:3).

    摘要翻译： 本发明涉及A系血凝素毒素肽，其是在编码这些肽的基因的信号序列和3'非翻译区与α-毒素肽序列中具有强同源性的芋螺毒素肽。 A系血凝素毒素肽包括下文进一步描述的α-毒素肽，α-毒素样肽和κ-毒素肽。 α-毒素 - 肽通常共有“核心”序列基序。 该核心序列称为α3/ 5核，并表示为Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys（SEQ ID NO：1）。 α-类毒素样肽通常共有称为α4/7核心的核心序列，并表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa -Cys（SEQ ID NO：2）。 κ-毒素肽通常具有称为kappa 7/2/1/3核心的核心序列，并且表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys -Xaa-Cys-Xaa-Xaa-Xaa-Cys（SEQ ID NO：3）。

    Contryphan peptides
    7.
    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
    10.
    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。