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Computational Design and Biological Evaluation of Analogs of Lupin Peptide P5 Endowed with Dual PCSK9/HMG-CoAR Inhibiting Activity

Pharmaceutics. 2022-03; 
Carmen Lammi, Enrico M A Fassi, Jianqiang Li, Martina Bartolomei, Giulia Benigno, Gabriella Roda, Anna Arnoldi, Giovanni Grazioso
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Proteins, Expression, Isolation and Analysis … The Genscript (Piscataway, NJ, USA) synthesized for us the P5 analogs selected for biological assays. All compounds are >95% pure by HPLC analysis (see Supporting Information for … Get A Quote

摘要

(1) Background: Proprotein convertase subtilisin/kexin 9 (PCSK9) is responsible for the degradation of the hepatic low-density lipoprotein receptor (LDLR), which regulates the circulating cholesterol level. In this field, we discovered natural peptides derived from lupin that showed PCSK9 inhibitory activity. Among these, the most active peptide, known as P5 (LILPHKSDAD), reduced the protein-protein interaction between PCSK9 and LDLR with an IC equals to 1.6 μM and showed a dual hypocholesterolemic activity, since it shows complementary inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR). (2) Methods: In this study, by a computational approach, the P5 primary structure was optimized to... More

關(guān)鍵詞

HMG-CoA reductase, MM-GBSA, PCSK9, drug design, dual activity, hypercholesterolemia, lupin, peptide
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