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

ABSTRACT: (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 IC₅₀ 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 obtain new analogs with improved affinity to PCSK9. Then, biologica

SUBMITTER: Lammi C 

PROVIDER: S-EPMC8951016 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature