文章基本信息

标题：Biological Characterization of Computationally Designed Analogs of peptide TVFTSWEEYLDWV (Pep2-8) with Increased PCSK9 Antagonistic Activity
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作者：Carmen Lammi ; Jacopo Sgrignani ; Anna Arnoldi 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-11
DOI：10.1038/s41598-018-35819-0
出版社：Springer Nature
摘要：The inhibition of the PCSK9/LDLR protein-protein interaction (PPI) is a promising strategy for developing new hypocholesterolemic agents. Recently, new antibodies have been approved for therapy, but the high cost and low patients' compliance stimulate the development of alternatives. Starting from the structural information available for the complex between PCSK9 and TVFTSWEEYLDWV (Pep2-8) peptide inhibitor and using computational methods, in this work we identified two Pep2-8 analogs as potential inhibitors of the PCSK9/LDLR PPI. Their biological characterization confirmed the theoretical outcomes. Remarkably, the treatment of HepG2 cells with these peptides increased the LDLR protein level on the cellular membrane, with activities that were 100 and 50 times better than the one of Pep2-8 tested at a 50 μM concentration. Moreover, they were 50 and 5 times more active than Pep2-8 in improving the functional ability of HepG2 cells to uptake extracellular LDL.