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    • 3. 发明授权
    • Peptide biosynthesis and pain therapy
    • 肽生物合成和疼痛治疗
    • US08003622B2
    • 2011-08-23
    • US12893255
    • 2010-09-29
    • Darren P. WolfeJoseph C. GloriosoDavid J. Fink
    • Darren P. WolfeJoseph C. GloriosoDavid J. Fink
    • A61K48/00C12N15/00
    • C07K5/1016A61K48/005C07K7/22C07K14/67C07K14/695C07K14/70C07K2319/50C07K2319/60C12N15/86C12N2710/16643G01N33/6893G01N33/9486G01N2800/2842
    • The invention provides an expression cassette comprising a DNA sequence encoding amino acids 1-99 of human preproenkephalin, a DNA sequence encoding a precursor of a carboxy-amidated peptide flanked by dibasic cleavage sites and optionally a DNA sequence encoding a marker protein (such as Enhanced Green Fluorescent Protein (GFP)) all in operable linkage and under control of a promoter. Where the encoded precursor of a carboxy-amidated peptide is an agonist for an opioid receptor, the invention further provides a method of treating neuropathic pain by administering the gene transfer vector comprising such an expression cassette to a patient. The invention also provides a method for detecting a peptide having a desired effect comprising introducing a library of DNA sequences encoding one or more precursors of carboxy-amidated peptides into host cells; expressing the carboxy-amidated peptides encoded in the library to provide expression products; and screening from the polypeptide expression products for the desired effect.
    • 本发明提供了一种表达盒,其包含编码人前脑啡肽的氨基酸1-99的DNA序列,编码侧翼为二碱基切割位点的羧基酰胺化肽的前体的DNA序列和任选的编码标记蛋白的DNA序列(例如增强型 绿色荧光蛋白(GFP))都在可操作的连锁和启动子的控制下。 当羧基酰胺化肽的编码前体是阿片受体的激动剂时,本发明还提供了通过将包含这种表达盒的基因转移载体给予患者来治疗神经性疼痛的方法。 本发明还提供了一种检测具有所需效果的肽的方法,包括将编码羧基酰胺化肽的一种或多种前体的DNA序列文库导入宿主细胞; 表达在文库中编码的羧基酰胺化肽以提供表达产物; 并从多肽表达产物筛选出所需的效果。
    • 4. 发明申请
    • PEPTIDE BIOSYNTHESIS AND PAIN THERAPY
    • 肽类生物化学和药物治疗
    • US20110112174A1
    • 2011-05-12
    • US12893255
    • 2010-09-29
    • Darren P. WolfeJoseph C. GloriosoDavid J. Fink
    • Darren P. WolfeJoseph C. GloriosoDavid J. Fink
    • A61K31/711A61P35/00A61P29/00A61P25/00A61P25/04
    • C07K5/1016A61K48/005C07K7/22C07K14/67C07K14/695C07K14/70C07K2319/50C07K2319/60C12N15/86C12N2710/16643G01N33/6893G01N33/9486G01N2800/2842
    • The invention provides an expression cassette comprising a DNA sequence encoding amino acids 1-99 of human preproenkephalin, a DNA sequence encoding a precursor of a carboxy-amidated peptide flanked by dibasic cleavage sites and optionally a DNA sequence encoding a marker protein (such as Enhanced Green Fluorescent Protein (GFP)) all in operable linkage and under control of a promoter. Where the encoded precursor of a carboxy-amidated peptide is an agonist for an opioid receptor, the invention further provides a method of treating neuropathic pain by administering the gene transfer vector comprising such an expression cassette to a patient. The invention also provides a method for detecting a peptide having a desired effect comprising introducing a library of DNA sequences encoding one or more precursors of carboxy-amidated peptides into host cells; expressing the carboxy-amidated peptides encoded in the library to provide expression products; and screening from the polypeptide expression products for the desired effect.
    • 本发明提供了一种表达盒,其包含编码人前脑啡肽的氨基酸1-99的DNA序列,编码侧翼为二碱基切割位点的羧基酰胺化肽的前体的DNA序列和任选的编码标记蛋白的DNA序列(例如增强型 绿色荧光蛋白(GFP))都在可操作的连锁和启动子的控制下。 当羧基酰胺化肽的编码前体是阿片受体的激动剂时,本发明还提供了通过将包含这种表达盒的基因转移载体给予患者来治疗神经性疼痛的方法。 本发明还提供了一种检测具有所需效果的肽的方法,包括将编码羧基酰胺化肽的一种或多种前体的DNA序列文库导入宿主细胞; 表达在文库中编码的羧基酰胺化肽以提供表达产物; 并从多肽表达产物筛选出所需的效果。