Cell-penetrating Chaperone Peptide Prevents Protein Aggregation And Protects Against Cell Apoptosis.
Cell-penetrating Chaperone Peptide Prevents Protein Aggregation And Protects Against Cell Apoptosis.
复制标题
细胞穿透伴侣肽可防止蛋白质聚集并防止细胞凋亡。
DOI：
10.1002/adbi.201700095
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发表时间：
2018
影响因子：
4.1
通讯作者：
Sharma,KKrishna
中科院分区：
文献类型：
--
作者：
Raju,Murugesan;Santhoshkumar,Puttur;Sharma,KKrishna
许多新发现的治疗性肽和分子由于不能穿过细胞膜而受到限制。在本研究中，一种细胞穿透肽（CPP）， VPTLK，来源于Ku70蛋白，被用来促进微型个体穿过细胞膜的进入。先前的研究表明，代表αA‐晶体蛋白伴侣位点的迷你伴侣肽可以抑制与蛋白质病变相关的蛋白质聚集，具有治疗潜力。通过将VPTLK序列与小伴侣蛋白的N端（FVIFLDVKHFSPEDLTVKGRD）融合制备合成的小伴侣蛋白，得到VPTLKFVIFLDVKHFSPEDLTVKGRD肽，称为“CPPGRD”。添加甘氨酸-精氨酸-天冬氨酸（GRD）氨基酸以增加肽的溶解度。使用醇脱氢酶和α‐乳清蛋白展开条件来测量CPPGRD的伴侣样功能。通过H2O2诱导的Cos - 7和ARPE - 19细胞凋亡实验来评估肽伴侣的抗凋亡作用。结果表明，CPPGRD具有伴侣功能和抗凋亡活性。此外，研究发现CPPGRD可防止β -淀粉样蛋白纤维形成并抑制β -淀粉样蛋白毒性。目前的研究表明，CPPGRD保护展开蛋白的聚集和防止细胞凋亡。因此，CPPGRD是一种有潜力成为蛋白质聚集性疾病治疗剂的小分子。
Many of the newly discovered therapeutic peptides and molecules are limited by their inability to cross the cell membrane. In the present study, a cell‐penetrating peptide (CPP), VPTLK, derived from Ku70 protein, is employed to facilitate the entry of a minichaperone across the cell membrane. Previous studies suggest that the minichaperone peptide representing the chaperone site in αA‐crystallin, which can inhibit protein aggregation associated with proteopathies, has therapeutic potential. A synthetic minichaperone is prepared by fusing the VPTLK sequence to N‐terminus of minichaperone (FVIFLDVKHFSPEDLTVKGRD) to get VPTLKFVIFLDVKHFSPEDLTVKGRD peptide, which is called “CPPGRD.” The amino acids, glycine–arginine–aspartic acid (GRD), are added to increase the solubility of the peptide. The chaperone‐like function of CPPGRD is measured using unfolding conditions for alcohol dehydrogenase and α‐lactalbumin. The antiapoptotic action of the peptide chaperone is evaluated using H2O2‐induced Cos‐7 and ARPE‐19 cell apoptosis assays. The results show that the CPPGRD has both chaperone function and antiapoptotic activity. Additionally, the CPPGRD is found to prevent β‐amyloid fibril formation and suppress β‐amyloid toxicity. The present study demonstrates that the CPPGRD protects unfolding proteins from aggregation and prevents cellular apoptosis. Therefore, the CPPGRD is a minichaperone with potential to become a therapeutic agent for protein aggregation diseases.