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    • 7. 发明授权
    • Bone morphogenetic protein antagonist based on the mature protein
    • 基于成熟蛋白的骨形态发生蛋白拮抗剂
    • US07132397B1
    • 2006-11-07
    • US09806368
    • 1999-10-04
    • Mieko KatsuuraMichio Kimura
    • Mieko KatsuuraMichio Kimura
    • A61K38/18C07K14/51
    • C07K14/51A61K38/00
    • The purpose is to provide a mature protein having an antagonistic activity against bone morphogenetic proteins. The mature protein having an antagonistic activity against bone morphogenetic proteins is obtained by converting at least one residue among methionine residues or tryptophane residues existing in the amino acid sequence of mature human MP52 (SEQ ID No 1) to a hydrophilic residue by chemical modification, or replacing said residues with a hydrophilic amino acid residue or a polar amino acid residue. The chemical modification for said methionine residue is performed by an oxidization reaction or an alkylation reaction. The chemical modification for said tryptophane residue is performed by an allylsulphenylation reaction. Or a mature protein having an antagonistic activity against bone morphogenetic proteins is obtained by converting at least one residue of tryptophane residues existing in the amino acid sequences of mature human BMP-2 (SEQ ID No 2), mature human BMP-4 (SEQ ID No 3), and mature human BMP-7 (SEQ ID No 4) to a hydrophilic residue by chemical modification, or replacing said residues with a hydrophilic amino acid residue or a polar amino acid residue.
    • 目的是提供对骨形态发生蛋白具有拮抗作用的成熟蛋白质。 通过化学修饰将成熟人MP52(SEQ ID No.1)的氨基酸序列中存在的甲硫氨酸残基或色氨酸残基中的至少一个残基转化成亲水性残基,获得对骨形态发生蛋白具有拮抗作用的成熟蛋白质,或 用亲水氨基酸残基或极性氨基酸残基取代所述残基。 所述甲硫氨酸残基的化学修饰通过氧化反应或烷基化反应进行。 所述色氨酸残基的化学修饰通过烯丙基苯基化反应进行。 或者通过转化成熟人BMP-2(SEQ ID No 2),成熟人BMP-4(SEQ ID No.2)的氨基酸序列中存在的色氨酸残基的至少一个残基,获得对骨形态发生蛋白具有拮抗活性的成熟蛋白质 No.3)和成熟的人BMP-7(SEQ ID No 4)通过化学修饰与亲水性残基反应,或用亲水氨基酸残基或极性氨基酸残基替代所述残基。