Series of Novel and Highly Potent Cyclic Peptide PCSK9 Inhibitors Derived from an mRNA Display Screen and Optimized via Structure-Based Design.
Animals
Cells, Cultured
Crystallography, X-Ray
/ methods
Drug Design
Enzyme Inhibitors
/ chemistry
Female
Humans
Macaca fascicularis
Male
Mice
Mice, Inbred C57BL
PCSK9 Inhibitors
Proprotein Convertase 9
/ chemistry
Protein Structure, Secondary
Protein Structure, Tertiary
RNA, Messenger
/ chemistry
Rats
Rats, Wistar
Structure-Activity Relationship
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
25 11 2020
25 11 2020
Historique:
pubmed:
11
11
2020
medline:
1
1
2021
entrez:
10
11
2020
Statut:
ppublish
Résumé
Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) is a key regulator of plasma LDL-cholesterol (LDL-C) and a clinically validated target for the treatment of hypercholesterolemia and coronary artery disease. In this paper, we describe a series of novel cyclic peptides derived from an mRNA display screen which inhibit the protein-protein interaction between PCSK9 and LDLR. Using a structure-based drug design approach, we were able to modify our original screening lead
Identifiants
pubmed: 33170686
doi: 10.1021/acs.jmedchem.0c01084
doi:
Substances chimiques
Enzyme Inhibitors
0
PCSK9 Inhibitors
0
RNA, Messenger
0
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM