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    • 2. 发明授权
    • Molecular conjugates containing cell membrane-blending agents
    • 含有细胞膜结合剂的分子结合体
    • US5149782A
    • 1992-09-22
    • US234399
    • 1988-08-19
    • Tse-wen ChangJean deVilliersWayne Gordon
    • Tse-wen ChangJean deVilliersWayne Gordon
    • A61K38/00A61K39/395A61K45/00A61K47/48
    • A61K47/48338A61K47/48238
    • Molecular conjugates which facilitate the attachment of macromolecular drugs onto cellular surfaces and their entry into cells are described. The molecular conjugates comprise a macromolecular drug linked to an "inactivated" membrane blending agent which inserts into the cellular plasma membrane. The membrane blending agent is inactivated by cleavable linkage to a blocking agent which, until released from the conjugate under appropriate conditions, blocks and ability of the membrane blending agent to insert into the cellular membrane. Upon release of the blocking agent, the membrane blending agent is "activated" and the conjugate can be inserted into a cellular plasma membrane. The membrane blending agents can be peptides such as fusogenic or ion channel forming peptides or long chain fatty acids. The blocking agents can be bulky or charged moieties which mask and prevent insertion of the membrane blending agent.
    • 描述了促进大分子药物附着到细胞表面上并进入细胞的分子共轭物。 分子共轭物包含与插入细胞质膜的“失活”膜共混剂连接的大分子药物。 膜共混剂通过可切割键与封闭剂失活,所述封闭剂直到在适当条件下从缀合物释放出来,并且膜共混剂插入细胞膜中的能力和能力。 在封闭剂释放后,膜共混剂被“活化”,并且缀合物可以插入到细胞质膜中。 膜共混剂可以是诸如融合或离子通道形成肽或长链脂肪酸的肽。 封闭剂可以是掩盖和防止膜共混剂插入的体积大或带电的部分。