[发明专利]改进的APOE类似物及其使用方法

摘要

本发明公开了新的ApoE肽衍生物和ApoE－蛋白转导结构域缀合物，它们可用于治疗包括CNS炎症、创伤性脑损伤、炎症性肠病(也称为节段性肠炎或溃疡性结肠炎)、脑缺血、动脉粥样硬化、败血症、多发性硬化和关节炎性疾病、阿尔茨海默氏症和其他脑部疾病在内的疾病。本发明包括通过施用ApoE或至少一种ApoE模拟肽而保护进行照射或放疗的对象的方法。

主权项

1.一种化合物，其含有选自如下一组的序列：LRVRLASH-(NMe)-L-RKLRKRLL-NH2 (SEQ ID NO.2)Ac-ASH-Aib-RKLRKRLL-NH2 (SEQ ID NO.3)Ac-AS-Aib-LRKLRKRLL-NH2 (SEQ ID NO.4)Ac-DS-Aib-LRKLRKRLL-NH2 (SEQ ID NO.5)Ac-ASHLRKL-Aib-KRLL-NH2 (SEQ ID NO.6)Ac-AS-Aib-LRKL-Aib-KRLL-NH2 (SEQ ID NO.7)Ac-DR-Aib-ASHLRKLRKR-Aib-L-NH2 (SEQ ID NO.8)Ac-DS-Aib-LRKLRKR-Aib-L-NH2 (SEQ ID NO.9)Ac-DR-Aib-ASHLRKL-Aib-KRLL-NH2 (SEQ ID NO.10)Ac-DS-Aib-LRKL-Aib-KRLL-NH2 (SEQ ID NO.11)Ac-DR-Aib-AS-Aib-LRKLRKRLL-NH2 (SEQ ID NO.12)Ac-DR-Aib-ASHLRKLRKRLL-NH2 (SEQ ID NO.13)Ac-CAS-Aib-LRKL-Aib-KRLL-NH2 (SEQ ID NO.14)Ac-DS-Aib-LRKL-Aib-KRLL-NH2 (SEQ ID NO.15)Ac-AS-Aib-LRKL-Aib-KRLV-NH2 (SEQ ID NO.16)Ac-AS-Aib-LRKL-Aib-KRLM-NH2 (SEQ ID NO.17)Ac-AS-Aib-LRKL-Aib-KRLI-NH2 (SEQ ID NO.18)Ac-AS-Aib-LRKL-Aib-KRLA-NH2 (SEQ ID NO.19)Ac-AS-Aib-LRKL-Aib-KALL-NH2 (SEQ ID NO.20)Ac-AS-Aib-LRKL-Aib-K(orn)LL-NH2 (SEQ ID NO.21)Ac-AS-Aib-LRKL-Aib-K(narg)LL-NH2 (SEQ ID NO.22)Ac-AS-Aib-LRKL-Aib-K(harg)LL-NH2 (SEQ ID NO.23)Ac-AS-Aib-LRKL-Aib-K(dmarg)LL-NH2 (SEQ ID NO.24)Ac-AS-Aib-LRKL-Aib-ARLL-NH2 (SEQ ID NO.25)Ac-AS-Aib-LRKL-Aib-(aclys)RLL-NH2 (SEQ ID NO.26)Ac-AS-Aib-LRKL-Aib-(azlys)RLL-NH2 (SEQ ID NO.27)Ac-ASH-Aib-RKL-Aib-KRLL-NH2 (SEQ ID NO.28)Ac-AS-Aib-LRKL-Aib-KRL-(NLe)-NH2 (SEQ ID NO.29)Ac-AS-Aib-LRKL-Aib-KR-(NLe)-L-NH2 (SEQ ID NO.30)Ac-AS-Aib-LRKL-Aib-KR-(NLe)-(Nle)-NH2 (SEQ ID NO.31)Ac-AS-Aib-LRKL-Aib-K(orn)L-(NLe)-NH2 (SEQ ID NO.32)Ac-AS-Aib-LRKL-Aib-K(orn)-(NLe)-L-NH2 (SEQ ID NO.33)Ac-AS-Aib-LRKL-Aib-K(orn)-(NLe)-(Nle)-NH2 (SEQ ID NO.34)Ac-AS-Aib-LRKL-Aib-K(harg)L-(NLe)-NH2 (SEQ ID NO.35)Ac-AS-Aib-LRKL-Aib-K(harg)-(NLe)-L-NH2 (SEQ ID NO.36)Ac-AS-Aib-LRKL-Aib-K(harg)-(NLe)-(Nle)-NH2 (SEQ ID NO.37)Ac-AS-Aib-L(orn)KL-Aib-KRLL-NH2 (SEQ ID NO.38)Ac-AS-Aib-L(orn)KL-Aib-K(orn)LL-NH2 (SEQ ID NO.39)Ac-AS-Aib-L(orn)KL-Aib-KRL-(NLe)-NH2 (SEQ ID NO.40)Ac-AS-Aib-L(orn)KL-Aib-KRL-(NLe)-(NLe)-NH2 (SEQ ID NO.41)Ac-AS-Aib-L(orn)KL-Aib-K(orn)L-(Nle)-NH2 (SEQ ID NO.42)Ac-AS-Aib-L(orn)KL-Aib-K(orn)-(NLe)-(Nle)-NH2 (SEQ ID NO.43)Ac-ASHLRKLRKRLL-NH2(apoe138-149) (SEQ ID NO.44)Ac-ASHCRKLCKRLL-NH2 (SEQ ID NO.45)Ac-ASCLRKLCKRLL-NH2 (SEQ ID NO.46)Ac-CSHLRKLCKRLL-NH2 (SEQ ID NO.47)Ac-ASHLRKCRKRCL-NH2 (SEQ ID NO.48)Ac-ASHCRKLRKRCL-NH2 (SEQ ID NO.49)。