[发明专利]芳香族阳离子肽及其用途

摘要

本公开内容提供了涉及芳香族阳离子肽的组合物和方法。该方法包括给有此需要的受试者施用有效量的芳香族阳离子肽。例如，该肽可施用于需要线粒体靶向抗氧化剂的受试者。

主权项

一种芳香族阳离子肽，所述芳香族阳离子肽选自下述：6‑丁酸CoQ0‑Phe‑D‑Arg‑Phe‑Lys‑NH₂6‑癸酸CoQ0‑Phe‑D‑Arg‑Phe‑Lys‑NH₂Arg‑Arg‑Dmt‑PheArg‑Cha‑LysArg‑DmtArg‑Dmt‑ArgArg‑Dmt‑LysArg‑Dmt‑Lys‑PheArg‑Dmt‑Lys‑Phe‑CysArg‑Dmt‑PheArg‑Dmt‑Phe‑LysArg‑Lys‑Dmt‑PheArg‑Lys‑Phe‑DmtArg‑Phe‑Dmt‑LysArg‑Phe‑LysArg‑Trp‑LysArg‑Tyr‑LysArg‑Tyr‑Lys‑PheD‑Arg‑D‑Dmt‑D‑Lys‑D‑Phe‑NH₂D‑Arg‑D‑Dmt‑D‑Lys‑L‑Phe‑NH₂D‑Arg‑D‑Dmt‑L‑Lys‑D‑Phe‑NH₂D‑Arg‑D‑Dmt‑L‑Lys‑L‑Phe‑NH₂D‑Arg‑Dmt‑D‑Lys‑NH₂D‑Arg‑Dmt‑D‑Lys‑Phe‑NH₂D‑Arg‑Dmt‑Lys‑D‑Phe‑NH₂D‑Arg‑Dmt–Lys‑NH₂D‑Arg‑Dmt‑Lys‑Phe‑CysD‑Arg‑Dmt‑NH₂D‑Arg‑L‑Dmt‑D‑Lys‑D‑Phe‑NH₂D‑Arg‑L‑Dmt‑D‑Lys‑L‑Phe‑NH₂D‑Arg‑L‑Dmt‑L‑Lys‑D‑Phe‑NH₂D‑Arg‑Phe‑Lys‑NH₂D‑Arg‑Trp‑Lys‑NH₂D‑Arg‑Tyr‑Lys‑NH₂Dmt‑ArgDmt‑LysDmt‑Lys‑D‑Phe‑NH₂Dmt‑Lys‑NH₂Dmt‑Lys‑PheDmt‑Lys‑PheDmt‑Lys‑Phe‑NH₂Dmt‑Phe‑Arg‑LysH‑Arg‑D‑Dmt‑Arg‑NH₂H‑Arg‑D‑Dmt‑Lys‑NH₂H‑Arg‑D‑Dmt‑Lys‑Phe‑NH₂H‑Arg‑D‑Dmt‑NH₂H‑Arg‑Dmt‑Lys‑Phe‑NH₂H‑D‑Arg‑2,6‑二氯‑L‑酪氨酸‑L‑Lys‑L‑Phe‑NH₂H‑D‑Arg‑2,6‑二氯酪氨酸‑Lys‑Phe‑NH₂H‑D‑Arg‑2,6‑二氟‑L‑酪氨酸‑L‑Lys‑L‑Phe‑NH₂H‑D‑Arg‑2,6‑二氟酪氨酸‑Lys‑Phe‑NH₂H‑D‑Arg‑2,6‑二甲基‑L‑苯丙氨酸‑L‑Lys‑L‑Phe‑NH₂H‑D‑Arg‑2,6‑二甲基苯丙氨酸‑Lys‑Phe‑NH₂H‑D‑Arg‑4‑甲氧基‑2,6‑二甲基‑L‑酪氨酸‑L‑Lys‑L‑Phe‑NH₂H‑D‑Arg‑4‑甲氧基‑2,6‑二甲基酪氨酸‑Lys‑Phe‑NH₂H‑D‑Arg‑Arg‑Dmt‑Phe‑NH₂H‑D‑Arg‑Cha‑Lys‑NH₂H‑D‑Arg‑D‑Dmt‑D‑Lys‑D‑Phe‑NH₂H‑D‑Arg‑D‑Dmt‑Lys‑Phe‑NH₂H‑D‑Arg‑D‑Dmt‑NH₂H‑D‑Arg‑Dmt‑D‑Lys‑D‑Phe‑NH₂H‑D‑Arg‑Dmt‑Lys‑2,6‑二甲基苯丙氨酸‑NH₂H‑D‑Arg‑Dmt‑Lys‑3‑羟基苯丙氨酸‑NH₂H‑D‑Arg‑Dmt‑Lys‑NH₂H‑D‑Arg‑Dmt‑Lys‑OHH‑D‑Arg‑Dmt‑Lys‑Phe‑OHH‑D‑Arg‑Dmt‑N6‑乙酰基赖氨酸‑Phe‑NH₂H‑D‑Arg‑Dmt‑OHH‑D‑Arg‑Dmt‑Phe‑Lys‑NH₂H‑D‑Arg‑Dmt‑Phe‑NH₂H‑D‑Arg‑D‑Phe‑L‑Lys‑L‑Phe‑NH₂H‑D‑Arg‑D‑Trp‑L‑Lys‑L‑Phe‑NH₂H‑D‑Arg‑D‑Tyr‑L‑Lys‑L‑Phe‑NH₂H‑D‑Arg‑L‑Dmt‑L‑Lys‑2,6‑二甲基‑L‑苯丙氨酸‑NH₂H‑D‑Arg‑L‑Dmt‑L‑Lys‑3‑羟基‑L‑苯丙氨酸‑NH₂H‑D‑Arg‑L‑Dmt‑L‑Lys‑D‑Dmt‑NH₂H‑D‑Arg‑L‑Dmt‑L‑Lys‑D‑Trp‑NH₂H‑D‑Arg‑L‑Dmt‑L‑Lys‑D‑Tyr‑NH₂H‑D‑Arg‑L‑Dmt‑L‑Lys‑L‑Dmt‑NH₂H‑D‑Arg‑L‑Dmt‑L‑Lys‑L‑Dmt‑NH₂H‑D‑Arg‑L‑Dmt‑L‑Lys‑L‑Trp‑NH₂H‑D‑Arg‑L‑Dmt‑L‑Lys‑L‑Tyr‑NH₂H‑D‑Arg‑L‑Dmt‑L‑Phe‑L‑Lys‑NH₂H‑D‑Arg‑L‑Dmt‑N6‑乙酰基‑L‑赖氨酸‑L‑Phe‑NH₂H‑D‑Arg‑L‑Lys‑L‑Dmt‑L‑Phe‑NH₂H‑D‑Arg‑L‑Lys‑L‑Phe‑L‑Dmt‑NH₂H‑D‑Arg‑L‑Phe‑L‑Dmt‑L‑Lys‑NH₂H‑D‑Arg‑L‑Phe‑L‑Lys‑L‑Dmt‑NH₂H‑D‑Arg‑L‑Phe‑L‑Lys‑L‑Phe‑NH₂H‑D‑Arg‑L‑Trp‑L‑Lys‑L‑Phe‑NH₂H‑D‑Arg‑L‑Tyr‑L‑Lys‑L‑Phe‑NH₂H‑D‑Arg‑Lys‑Dmt‑Phe‑NH₂H‑D‑Arg‑Lys‑Phe‑Dmt‑NH₂H‑D‑Arg‑Phe‑Dmt‑Lys‑NH₂H‑D‑Arg‑Phe‑Lys‑Dmt‑NH₂H‑D‑Arg‑Tyr‑Lys‑Phe‑NH₂H‑D‑Dmt‑Arg‑NH₂H‑D‑His‑L‑Dmt‑L‑Lys‑L‑Phe‑NH₂H‑D‑Lys‑L‑Dmt‑L‑Lys‑L‑Phe‑NH₂H‑Dmt‑D‑Arg‑Lys‑Phe‑NH₂H‑Dmt‑D‑Arg‑NH₂H‑Dmt‑D‑Arg‑Phe‑Lys‑NH₂H‑Dmt‑D‑Phe‑Arg‑Lys‑NH₂H‑Dmt‑Lys‑D‑Arg‑Phe‑NH₂H‑Dmt‑Lys‑Phe‑D‑Arg‑NH₂H‑Dmt‑Phe‑D‑Arg‑Lys‑NH₂H‑Dmt‑Phe‑Lys‑D‑Arg‑NH₂H‑D‑N2‑乙酰基精氨酸‑Dmt‑Lys‑Phe‑NH₂H‑D‑N8‑乙酰基精氨酸‑Dmt‑Lys‑Phe‑NH₂H‑D‑Phe‑D‑Arg‑D‑Phe‑D‑Lys‑NH₂H‑L‑Dmt‑D‑Arg‑L‑Lys‑L‑Phe‑NH₂H‑L‑Dmt‑D‑Arg‑L‑Phe‑L‑Lys‑NH₂H‑L‑Dmt‑L‑Lys‑D‑Arg‑L‑Phe‑NH₂H‑L‑Dmt‑L‑Lys‑L‑Phe‑D‑Arg‑NH₂H‑L‑Dmt‑L‑Phe‑D‑Arg‑L‑Lys‑NH₂H‑L‑Dmt‑L‑Phe‑L‑Lys‑D‑Arg‑NH₂H‑L‑His‑L‑Dmt‑L‑Lys‑L‑Phe‑NH₂H‑L‑Lys‑D‑Arg‑L‑Dmt‑L‑Phe‑NH₂H‑L‑Lys‑D‑Arg‑L‑Phe‑L‑Dmt‑NH₂H‑L‑Lys‑L‑Dmt‑D‑Arg‑L‑Phe‑NH₂H‑L‑Lys‑L‑Dmt‑L‑Lys‑L‑Phe‑NH₂H‑L‑Lys‑L‑Dmt‑L‑Phe‑D‑Arg‑NH₂H‑L‑Lys‑L‑Phe‑D‑Arg‑L‑Dmt‑NH₂H‑L‑Lys‑L‑Phe‑L‑Dmt‑D‑Arg‑NH₂H‑L‑Phe‑D‑Arg‑L‑Dmt‑L‑Lys‑NH₂H‑L‑Phe‑D‑Arg‑L‑Lys‑L‑Dmt‑NH₂H‑L‑Phe‑L‑Dmt‑D‑Arg‑L‑Lys‑NH₂H‑L‑Phe‑L‑Dmt‑L‑Lys‑D‑Arg‑NH₂H‑L‑Phe‑L‑Lys‑D‑Arg‑L‑Dmt‑NH₂H‑L‑Phe‑L‑Lys‑L‑Dmt‑D‑Arg‑NH₂H‑Lys‑D‑Arg‑Dmt‑Phe‑NH₂H‑Lys‑D‑Arg‑Phe‑Dmt‑NH₂H‑Lys‑Dmt‑D‑Arg‑Phe‑NH₂H‑Lys‑Dmt‑Phe‑D‑Arg‑NH₂H‑Lys‑D‑Phe‑Arg‑Dmt‑NH₂H‑Lys‑Phe‑D‑Arg‑Dmt‑NH₂H‑Lys‑Phe‑Dmt‑D‑Arg‑NH₂H‑N2‑乙酰基‑D‑精氨酸‑L‑Dmt‑L‑Lys‑L‑Phe‑NH₂H‑N7‑乙酰基‑D‑精氨酸‑Dmt‑Lys‑Phe‑NH₂H‑Phe(d5)‑D‑Arg‑Phe(d5)‑Lys‑NH₂H‑Phe‑Arg‑Phe‑Lys‑NH₂H‑Phe‑D‑Arg‑Dmt‑Lys‑NH₂H‑Phe‑D‑Arg‑Dmt‑Lys‑NH₂H‑Phe‑D‑Arg‑D‑Phe‑Lys‑NH₂H‑Phe‑D‑Arg‑Lys‑Dmt‑NH₂H‑Phe‑D‑Arg‑Phe‑D‑Lys‑NH₂H‑Phe‑D‑Arg‑Phe‑Lys‑Glu‑Cys‑Gly‑NH₂H‑Phe‑D‑Dmt‑Arg‑Lys‑NH₂H‑Phe‑Dmt‑D‑Arg‑Lys‑NH₂H‑Phe‑Dmt‑Lys‑D‑Arg‑NH₂H‑Phe‑Lys‑D‑Arg‑Dmt‑NH₂H‑Phe‑Lys‑Dmt‑D‑Arg‑NH₂L‑Arg‑D‑Dmt‑D‑Lys‑D‑Phe‑NH₂L‑Arg‑D‑Dmt‑D‑Lys‑D‑Phe‑NH₂L‑Arg‑D‑Dmt‑D‑Lys‑L‑Phe‑NH₂L‑Arg‑D‑Dmt‑D‑Lys‑L‑Phe‑NH₂L‑Arg‑D‑Dmt‑L‑Lys‑D‑Phe‑NH₂L‑Arg‑D‑Dmt‑L‑Lys‑D‑Phe‑NH₂L‑Arg‑D‑Dmt‑L‑Lys‑L‑Phe‑NH₂L‑Arg‑D‑Dmt‑L‑Lys‑L‑Phe‑NH₂L‑Arg‑L‑Dmt‑D‑Lys‑D‑Phe‑NH₂L‑Arg‑L‑Dmt‑D‑Lys‑D‑Phe‑NH₂L‑Arg‑L‑Dmt‑D‑Lys‑L‑Phe‑NH₂L‑Arg‑L‑Dmt‑D‑Lys‑L‑Phe‑NH₂L‑Arg‑L‑Dmt‑L‑Lys‑D‑Phe‑NH₂L‑Arg‑L‑Dmt‑L‑Lys‑D‑Phe‑NH₂L‑Arg‑L‑Dmt‑L‑Lys‑L‑Phe‑NH₂L‑Arg‑L‑Dmt‑L‑Lys‑L‑Phe‑NH₂Lys‑Dmt‑ArfLys‑Dmt‑D‑Arg‑NH₂Lys‑PheLys‑Phe‑Arg‑DmtLys‑Phe‑NH₂Lys‑Trp‑ArgLys‑Trp‑D‑Arg‑NH₂Phe‑Arg‑Dmt‑LysPhe‑Arg‑Phe‑LysPhe‑Arg‑Phe‑LysPhe‑Arg‑Phe‑LysPhe‑Arg‑Phe‑LysPhe‑Arg‑Phe‑LysPhe‑Arg‑Phe‑Lys‑Glu‑Cys‑GlyPhe‑Dmt‑Arg‑LysPhe‑Lys‑DmtPhe‑Lys‑Dmt‑NH₂琥珀酸单酯CoQ0‑Phe‑D‑Arg‑Phe‑Lys‑NH₂