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)。
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)。
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。
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)。
摘要:
The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr10-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.
摘要:
The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr10-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.
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:
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.
摘要:
The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr10-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.
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.