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1.发明申请Enzymatic electrochemical detection assay using protective monolayer and device therefor 审中-公开使用保护性单层的酶电化学检测测定及其设备公开(公告)号：US20060160100A1
公开(公告)日：2006-07-20
申请号：US11038289
申请日：2005-01-19
申请人： Zhiqiang Gao , Ponnampalam Gopalakrishnakone , Van Le , Fang Xie
发明人： Zhiqiang Gao , Ponnampalam Gopalakrishnakone , Van Le , Fang Xie
CPC分类号： B82Y15/00 , B82Y30/00 , C12Q1/6825 , G01N33/5438 , C12Q2565/607 , C12Q2563/113
摘要： There is provided an electrochemical assay method for detecting a target molecule, for example a protein, in a sample, which involves the use of a protective monolayer and a redox polymer to form a bilayer immobilized on an electrode. The monolayer protects the electrode from non-specific adherence of reagents, particular proteins, to the electrode while simultaneously providing a surface that can be functionalized to immobilize a capture molecule and that can interact with the redox polymer.
摘要翻译： 提供了用于检测样品中的靶分子例如蛋白质的电化学测定方法，其涉及使用保护性单层和氧化还原聚合物以形成固定在电极上的双层。 单层保护电极免受试剂，特定蛋白质对电极的非特异性粘附，同时提供可以被官能化以固定捕获分子并且可与氧化还原聚合物相互作用的表面。
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2.发明授权Phospholipase A2-inhibitory peptide with anti-arthritic and neuroprotective activities 有权具有抗关节炎和神经保护活性的磷脂酶A2抑制肽公开(公告)号：US07176281B2
公开(公告)日：2007-02-13
申请号：US10836825
申请日：2004-04-30
摘要： Peptides that have potent PLA2-inhibitory activity are disclosed. Homology searches of known PLA inhibitory molecules were used to identify and subsequently design potent peptide molecules that can induce neuroprotective as well as anti-inflammatory effect. These peptides were shown to protect against degeneration of joints in transgenic mouse model prone to arthritis. Protection from kainate-induced excitotoxic neuronal injury was also observed using these peptides. These peptides, their analogs and derivatives have potential as neuroprotective and/or anti-inflammatory agents in a clinical setting.
摘要翻译： 公开了具有有效的PLA 2 - 抑制活性的肽。 已知PLA抑制分子的同源性检索用于鉴定并随后设计可诱导神经保护作用以及抗炎作用的有效肽分子。 显示这些肽可以防止易于发生关节炎的转基因小鼠模型中关节的变性。 使用这些肽也观察到保护免受红藻氨酸诱发的兴奋性毒性神经元损伤。 这些肽，其类似物和衍生物在临床环境中具有作为神经保护和/或抗炎剂的潜力。
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公开(公告)号：US07579433B2
公开(公告)日：2009-08-25
申请号：US11414719
申请日：2006-04-28
摘要： The present invention provides a new 18-residue homodimerized peptide, designated PIP [59-67] dimer (SEQ ID NO: 1), which is a mutant of the optimized anti-inflammatory peptide P-NT.II, the patent for which has recently been filed [1]. P-NT.II has the potential to modulate both the inflammatory and bone damaging components of rheumatoid arthritis, and was originally designed on the basis of the primary structure of the anti-inflammatory protein termed ‘Phospholipase Inhibitor from Python (PIP)’ [2]. Using solid phase chemistry, variants of P-NT.II were designed and examined for inhibitory activity against secretory phospholipase A2 (sPLA2), a key enzyme involved in the inflammatory pathway, and matrix metalloproteinases (MMPs) that are involved in the remodeling and degradation of the extracellular matrix in rheumatoid arthritis (RA) and cancer. Among the family of mutants tested, the dimerized peptide was found to be the most potent inhibitor against sPLA2 as well as the human recombinant MMP-1. This invention provides the utility of the peptide analogue PIP [59-67] dimer as a potential therapeutic agent for modulation of inflammatory diseases such as rheumatoid arthritis, and cancer. This invention relates to all the polypeptide analogues (SEQ ID NO: 1 to 3) and polynucleotides (SEQ ID NO: 4), and to the use of those polypeptides and polynucleotides, their synthetic chemical analogues or variants that inhibit activity and synthesis of sPLA2 and MMPs, in the diagnosis, study, prevention and treatment of rheumatoid arthritis and/or cancer.
摘要翻译： 本发明提供了一种称为PIP [59-67]二聚体（SEQ ID NO：1）的新的18残基同源二聚体肽，其是优化的抗炎肽P-NT.II的突变体，其专利具有 最近被提交[1]。 P-NT.II具有调节类风湿性关节炎的炎性和骨损伤成分的潜力，并且最初是基于称为“来自Python（PIP）的磷脂酶抑制剂”的抗炎蛋白质的一级结构设计的[2 ]。 使用固相化学，设计了P-NT.II的变体，并检测了与分泌性磷脂酶A2（sPLA2）（参与炎症途径的关键酶）和参与重塑和降解的基质金属蛋白酶（MMP）的抑制活性 的类风湿关节炎（RA）和癌症中的细胞外基质。 在测试的突变体家族中，发现二聚化肽是针对sPLA2以及人重组MMP-1的最有效的抑制剂。 本发明提供了肽类似物PIP [59-67]二聚体作为调节炎性疾病如类风湿性关节炎和癌症的潜在治疗剂的用途。 本发明涉及所有多肽类似物（SEQ ID NO：1至3）和多核苷酸（SEQ ID NO：4），以及这些多肽和多核苷酸的合成化学类似物或变体，其抑制sPLA2的活性和合成 和MMPs在类风湿性关节炎和/或癌症的诊断，研究，预防和治疗中的应用。
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公开(公告)号：US07094575B2
公开(公告)日：2006-08-22
申请号：US10163499
申请日：2002-06-07
申请人： Ponnampalam Gopalakrishnakone , Maung-Maung Thwin , Kandiah Jeyaseelan , Arunmozhiarasi Armugam
发明人： Ponnampalam Gopalakrishnakone , Maung-Maung Thwin , Kandiah Jeyaseelan , Arunmozhiarasi Armugam
IPC分类号： C12N15/09
CPC分类号： C07K14/46 , A61K38/00 , C12Q1/34 , G01N33/6893 , G01N2333/4609 , G01N2333/914 , G01N2800/42
摘要： A phospholipase A2 inhibitor protein designated “Phospholipase Inhibitor from Python” (PIP)—formerly designated “Python Antitoxic Factor” (PAF)—is given by SEQ ID NO:2. The partial amino acid sequence for PIP was initially determined from the native protein purified from the blood serum of a non-venomous snake, Python reticulatus. The complete PIP polynucleotide sequence was obtained from a cDNA clone encoding PIP, given by SEQ ID NO:1, along with the full amino acid sequence deduced from it. Also disclosed is a recombinant protein PIP, which shows strong lethal toxin neutralizing activity similar to the native PIP, and has potent anti-inflammatory activity. Both the native and the functionally equivalent recombinant PIP are useful for the prevention or treatment of conditions such as snakebites, insect stings, and inflammatory diseases. Also, phospholipase A2 (PLA2) inhibitory polypeptides designated P-0029, P-0009, and P-0006, the sequences of which are given as SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, respectively, are disclosed. Those polypeptides, and their synthetic chemical analogues and polypeptide variants that inhibit PLA2 activity and alleviate inflammation, may also be used in the diagnosis, study, prevention, and treatment of PLA2-related human inflammatory diseases.
摘要翻译： 由SEQ ID NO：2给出的称为“Python抗氧化因子”（PAF）的称为“来自Python的磷脂酶抑制剂”（PIP）的磷脂酶A 2 N抑制剂蛋白质。 PIP的部分氨基酸序列最初是从从非毒蛇蛇纹状体的血清中纯化的天然蛋白质来确定的。 从编码PIP的cDNA克隆获得完整的PIP多核苷酸序列，由SEQ ID NO：1给出，以及从其推导出的完整氨基酸序列。 还公开了重组蛋白PIP，其显示出与天然PIP类似的强致死毒素中和活性，并且具有有效的抗炎活性。 天然和功能等同的重组PIP都可用于预防或治疗诸如蛇咬伤，昆虫叮咬和炎性疾病的病症。 另外，称为P-0029，P-0009和P-0006的磷脂酶A 2（PLA 2 H 2）抑制性多肽，其序列如SEQ ID NO： 10，SEQ ID NO：11和SEQ ID NO：12。 抑制PLA 2活性和减轻炎症的那些多肽及其合成的化学类似物和多肽变体也可以用于诊断，研究，预防和治疗PLA2 相关人类炎症性疾病。
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公开(公告)号：US20060078551A1
公开(公告)日：2006-04-13
申请号：US11289494
申请日：2005-11-30
申请人： Ponnampalam Gopalakrishnakone , Maung-Maung Thwin , Kandiah Jey Aseelan , Arunmozhiarasi Armugam
发明人： Ponnampalam Gopalakrishnakone , Maung-Maung Thwin , Kandiah Jey Aseelan , Arunmozhiarasi Armugam
CPC分类号： C07K14/46 , A61K38/00 , C12Q1/34 , G01N33/6893 , G01N2333/4609 , G01N2333/914 , G01N2800/42
摘要： A phospholipase A2 inhibitor protein designated “Phospholipase Inhibitor from Python” (PIP)—formerly designated “Python Antitoxic Factor” (PAF)—is given by SEQ ID NO:2. The partial amino acid sequence for PIP was initially determined from the native protein purified from the blood serum of a non-venomous snake, Python reticulatus. The complete PIP polynucleotide sequence was obtained from a cDNA clone encoding PIP, given by SEQ ID NO:1, along with the full amino acid sequence deduced from it. Also disclosed is a recombinant protein PIP, which shows strong lethal toxin neutralizing activity similar to the native PIP, and has potent anti-inflammatory activity. Both the native and the functionally equivalent recombinant PIP are useful for the prevention or treatment of conditions such as snakebites, insect stings, and inflammatory diseases. Also, phospholipase A2 (PLA2) inhibitory polypeptides designated P-0029, P-0009, and P-0006, the sequences of which are given as SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, respectively, are disclosed. Those polypeptides, and their synthetic chemical analogues and polypeptide variants that inhibit PLA2 activity and alleviate inflammation, may also be used in the diagnosis, study, prevention, and treatment of PLA2-related human inflammatory diseases.
摘要翻译： 由SEQ ID NO：2给出的称为“Python抗氧化因子”（PAF）的称为“来自Python的磷脂酶抑制剂”（PIP）的磷脂酶A 2 N抑制剂蛋白质。 PIP的部分氨基酸序列最初是从从非毒蛇蛇纹状体的血清中纯化的天然蛋白质来确定的。 从编码PIP的cDNA克隆获得完整的PIP多核苷酸序列，由SEQ ID NO：1给出，以及从其推导出的完整氨基酸序列。 还公开了重组蛋白PIP，其显示出与天然PIP类似的强致死毒素中和活性，并且具有有效的抗炎活性。 天然和功能等同的重组PIP都可用于预防或治疗诸如蛇咬伤，昆虫叮咬和炎性疾病的病症。 另外，称为P-0029，P-0009和P-0006的磷脂酶A 2（PLA 2 H 2）抑制性多肽，其序列如SEQ ID NO： 10，SEQ ID NO：11和SEQ ID NO：12。 抑制PLA 2活性和减轻炎症的那些多肽及其合成的化学类似物和多肽变体也可以用于诊断，研究，预防和治疗PLA2 相关人类炎症性疾病。
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公开(公告)号：US06613745B1
公开(公告)日：2003-09-02
申请号：US09530799
申请日：2000-07-26
申请人： Ponnampalam Gopalakrishnakone , Xiao Chun Pu , Peter Tsun-Hon Wong , Mathew Choon Eng Gwee , R. Manjunatha Kini
发明人： Ponnampalam Gopalakrishnakone , Xiao Chun Pu , Peter Tsun-Hon Wong , Mathew Choon Eng Gwee , R. Manjunatha Kini
IPC分类号： A61K3800
摘要： The present invention relates generally to peptide molecules and to derivatives, homologues, analogues and mimetics thereof capable of inducing or facilitating analgesia or partial analgesia alone or in combination with other analgesic molecules. The present invention also contemplates a method of inducing or facilitating analgesia or partial analgesia by the administration of a peptide or a derivative, homologue, analogue or mimetic thereof. The amino acid sequence of the peptide molecules of the present invention are derived from or based on amino acid sequences of snake venom toxins, and, in particular, &agr;-neurotoxins.
摘要翻译： 本发明一般涉及能够诱导或促进单独镇痛或部分止痛或与其它止痛分子组合的衍生物，同系物，类似物和模拟物。 本发明还考虑通过给予肽或其衍生物，同系物，类似物或模拟物诱导或促进镇痛或部分镇痛的方法。 本发明的肽分子的氨基酸序列衍生自或基于蛇毒毒素，特别是α-神经毒素的氨基酸序列。
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公开(公告)号：US07422890B2
公开(公告)日：2008-09-09
申请号：US11289494
申请日：2005-11-30
申请人： Ponnampalam Gopalakrishnakone , Maung-Maung Thwin , Kandiah Jeyaseelan , Arunmozhiarasi Armugam
发明人： Ponnampalam Gopalakrishnakone , Maung-Maung Thwin , Kandiah Jeyaseelan , Arunmozhiarasi Armugam
CPC分类号： C07K14/46 , A61K38/00 , C12Q1/34 , G01N33/6893 , G01N2333/4609 , G01N2333/914 , G01N2800/42
摘要： A phospholipase A2 inhibitor protein designated “Phospholipase Inhibitor from Python” (PIP)—formerly designated “Python Antitoxic Factor” (PAF)—is given by SEQ ID NO:2. The partial amino acid sequence for PIP was initially determined from the native protein purified from the blood serum of a non-venomous snake, Python reticulatus. The complete PIP polynucleotide sequence was obtained from a cDNA clone encoding PIP, given by SEQ ID NO:1, along with the full amino acid sequence deduced from it. Also disclosed is a recombinant protein PIP, which shows strong lethal toxin neutralizing activity similar to the native PIP, and has potent anti-inflammatory activity. Both the native and the functionally equivalent recombinant PIP are useful for the prevention or treatment of conditions such as snakebites, insect stings, and inflammatory diseases. Also, phospholipase A2 (PLA2) inhibitory polypeptides designated P-0029, P-0009, and P-0006, the sequences of which are given as SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, respectively, are disclosed. Those polypeptides, and their synthetic chemical analogues and polypeptide variants that inhibit PLA2 activity and alleviate inflammation, may also be used in the diagnosis, study, prevention, and treatment of PLA2-related human inflammatory diseases.
摘要翻译： 由SEQ ID NO：2给出的称为“Python抗氧化因子”（PAF）的称为“来自Python的磷脂酶抑制剂”（PIP）的磷脂酶A 2 N抑制剂蛋白质。 PIP的部分氨基酸序列最初是从从非毒蛇蛇纹状体的血清中纯化的天然蛋白质来确定的。 从编码PIP的cDNA克隆获得完整的PIP多核苷酸序列，由SEQ ID NO：1给出，以及从其推导出的完整氨基酸序列。 还公开了重组蛋白PIP，其显示出与天然PIP类似的强致死毒素中和活性，并且具有有效的抗炎活性。 天然和功能等同的重组PIP都可用于预防或治疗诸如蛇咬伤，昆虫叮咬和炎性疾病的病症。 另外，称为P-0029，P-0009和P-0006的磷脂酶A 2（PLA 2 H 2）抑制性多肽，其序列如SEQ ID NO： 10，SEQ ID NO：11和SEQ ID NO：12。 抑制PLA 2活性和减轻炎症的那些多肽及其合成的化学类似物和多肽变体也可以用于诊断，研究，预防和治疗PLA2 相关人类炎症性疾病。
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公开(公告)号：US20070128179A1
公开(公告)日：2007-06-07
申请号：US11594173
申请日：2006-11-08
CPC分类号： C12N9/20 , A61K38/00 , C12Y301/01004 , Y02A50/473
摘要： The present invention provides a method for the treatment and/or prevention of a bacterial related condition comprising administering to a subject a therapeutically effective amount of at least one phospholipase, isoform, derivative, mutant and/or fragment thereof. The phospholipase, isoform, derivative, mutant and/or fragment thereof, may be obtained from at least one venom selected from the group consisting of: Daboia russelli russelli, Daboia russelli siamensis, Daboia russelli pulchella, Crotalus adamanteus, Crotalus durissus terrificus, Pseudechis australis, Agkistrodon halys, Pseudechis guttata, Bitis arietans, Bitis gabonica rhinoceros, Echis carinatus, Acanthopis antarticus, Bungarus candidus, Bothrops asper, Bothrops jararacussu and/or Apis mellifera. The present invention also provides isolated peptides comprising at least one amino acid sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:2, an isoform, derivative, mutant and/or fragment thereof.
摘要翻译： 本发明提供了治疗和/或预防细菌相关病症的方法，包括向受试者施用治疗有效量的至少一种磷脂酶，同种型，衍生物，突变体和/或片段。 磷脂酶，同种型，衍生物，突变体和/或片段可以从至少一种选自以下的毒液获得：Daboia russelli russelli，Daboia russelli siamensis，Daboia russelli pulchella，Crotalus adamanteus，Crotalus durissus terrificus，Pseudechis australis Ag，，Ag，ata ata，，rh，，atus，，us，，，，，，，jar or or or。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。。 本发明还提供了分离的肽，其包含至少一个选自SEQ ID NO：1，SEQ ID NO：2，其同种型，衍生物，突变体和/或片段的氨基酸序列。
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公开(公告)号：US20070037253A1
公开(公告)日：2007-02-15
申请号：US11414719
申请日：2006-04-28
摘要： The present invention provides a new 18-residue homodimerized peptide, designated PIP [59-67] dimer (SEQ ID NO: 1), which is a mutant of the optimized anti-inflammatory peptide P-NT.II, the patent for which has recently been filed [1]. P-NT.II has the potential to modulate both the inflammatory and bone damaging components of rheumatoid arthritis, and was originally designed on the basis of the primary structure of the anti-inflammatory protein termed ‘Phospholipase Inhibitor from Python (PIP)’ [2]. Using solid phase chemistry, variants of P-NT.II were designed and examined for inhibitory activity against secretory phospholipase A2 (sPLA2), a key enzyme involved in the inflammatory pathway, and matrix metalloproteinases (MMPS) that are involved in the remodeling and degradation of the extracellular matrix in rheumatoid arthritis (RA) and cancer. Among the family of mutants tested, the dimerized peptide was found to be the most potent inhibitor against sPLA2 as well as the human recombinant MMP-1. This invention provides the utility of the peptide analogue PIP [59-67] dimer as a potential therapeutic agent for modulation of inflammatory diseases such as rheumatoid arthritis, and cancer. This invention relates to all the polypeptide analogues (SEQ ID NO: 1 to 3) and polynucleotides (SEQ ID NO: 4), and to the use of those polypeptides and polynucleotides, their synthetic chemical analogues or variants that inhibit activity and synthesis of sPLA2 and MMPs, in the diagnosis, study, prevention and treatment of rheumatoid arthritis and/or cancer.
摘要翻译： 本发明提供了一种称为PIP [59-67]二聚体（SEQ ID NO：1）的新的18残基同源二聚体肽，其是优化的抗炎肽P-NT.II的突变体，其专利具有 最近被提交[1]。 P-NT.II具有调节类风湿性关节炎的炎性和骨损伤成分的潜力，并且最初是基于称为“来自Python（PIP）的磷脂酶抑制剂”的抗炎蛋白质的一级结构设计的[2 ]。 使用固相化学，设计了P-NT.II的变体，并检测了与分泌性磷脂酶A2（sPLA2）（参与炎症途径的关键酶）和参与重塑和降解的基质金属蛋白酶（MMPS）的抑制活性 的类风湿性关节炎（RA）和癌症中的细胞外基质。 在测试的突变体家族中，发现二聚化肽是针对sPLA2以及人重组MMP-1的最有效的抑制剂。 本发明提供了肽类似物PIP [59-67]二聚体作为调节炎性疾病如类风湿性关节炎和癌症的潜在治疗剂的用途。 本发明涉及所有多肽类似物（SEQ ID NO：1至3）和多核苷酸（SEQ ID NO：4），以及这些多肽和多核苷酸的合成化学类似物或变体，其抑制sPLA2的活性和合成 和MMPs在类风湿性关节炎和/或癌症的诊断，研究，预防和治疗中的应用。
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公开(公告)号：US20060222638A1
公开(公告)日：2006-10-05
申请号：US10559649
申请日：2004-06-04
申请人： Kandiah Jeyaseelan , Arunmozhiarasi Armugam , Siaw Chai , Prabhakaran Ramkishen , Ponnampalam Gopalakrishnakone , Kwon Huat Tan
发明人： Kandiah Jeyaseelan , Arunmozhiarasi Armugam , Siaw Chai , Prabhakaran Ramkishen , Ponnampalam Gopalakrishnakone , Kwon Huat Tan
CPC分类号： C07K14/81 , A61K38/00 , C07K14/43522
摘要： An isolated peptide comprising the amino acid sequence of SEQ ID NO: 2, or a variant, derivative and/or fragment thereof having the function of HMGCoA reductase inhibitor, phosphomevalonate inhibitor, reducing the accumulation of cholesterol in the cholesterol biosynthesis pathway and/or reducing the level of serum cholesterol. Also disclosed is a pharmaceutical composition comprising the peptide having sequence SEQ ID NO:2 or a variant, derivative and/or fragment thereof. Also disclosed is a method for treatment or prophylaxis of disorders characterised by the accumulation of cholesterol, its by-products and/or related lipid derived products, comprising administering to a subject in need at least one peptide comprising the amino acid sequence of SEQ ID NO: 2, or a variant, derivative and/or fragment thereof.
摘要翻译： 包含SEQ ID NO：2的氨基酸序列的分离的肽，或其具有HMGCoA还原酶抑制剂，磷酸梅氨酸盐抑制剂的功能的变体，衍生物和/或片段，减少胆固醇在胆固醇生物合成途径中的积累和/或还原 血清胆固醇水平。 还公开了包含具有序列SEQ ID NO：2的肽或其变体，衍生物和/或片段的药物组合物。 还公开了一种用于治疗或预防特征在于胆固醇及其副产物和/或相关的脂质衍生产物的积累的疾病的方法，其包括向需要的受试者施用至少一种包含SEQ ID NO的氨基酸序列的肽 ：2，或其变体，衍生物和/或片段。
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