Disrupting the PCSK9/LDLR protein–protein interaction by an imidazole-based minimalist peptidomimetic. Issue 41 (6th October 2016)

• Record Type: Journal Article
• Authors: Stucchi, Mattia; Grazioso, Giovanni; Lammi, Carmen; Manara, Silvia; Zanoni, Chiara; Arnoldi, Anna; Lesma, Giordano; Silvani, Alessandra
• Is Part Of: Organic & biomolecular chemistry. Volume 14:Issue 41(2016)
• Page Start: 9736
• Page End: 9740
• Publication Date: 2016-10-06
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c6ob01642a
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : We report on a tetraimidazole-based β-strand minimalist peptidomimetic as a novel inhibitor of LDLR–PCSK9 protein–protein interaction, a promising target for hypercholesterolemia. Abstract : Herein we report on the multicomponent synthesis of a novel imidazole-based compound, able to act efficiently as a minimalist β-strand mimic. Biological evaluation proved its ability to impair the LDLR–PCSK9 protein–protein interaction, disclosing it as the first small molecule exerting a PCSK9-mediated hypocholesterolemic effect.