title: Disrupting the PCSK9/LDLR protein-protein interaction by an imidazole-based minimalist peptidomimetic.
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.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy. mattia.stucchi@unimi.it and Dipartimento di Scienze della Vita, Università di Modena e Reg-gio Emilia, via G. Campi 103, 41125 Modena, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Stucchi
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milano, Italy. giovanni.grazioso@unimi.it carmen.lammi@unimi.it.
authors.forename: Giovanni
authors.identifier: http://orcid.org/0000-0002-3261-9356
authors.initials: G
authors.lastname: Grazioso
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milano, Italy. giovanni.grazioso@unimi.it carmen.lammi@unimi.it.
authors.forename: Carmen
authors.initials: C
authors.lastname: Lammi
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milano, Italy. giovanni.grazioso@unimi.it carmen.lammi@unimi.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Manara
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milano, Italy. giovanni.grazioso@unimi.it carmen.lammi@unimi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Zanoni
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milano, Italy. giovanni.grazioso@unimi.it carmen.lammi@unimi.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Arnoldi
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy. mattia.stucchi@unimi.it.
authors.forename: Giordano
authors.initials: G
authors.lastname: Lesma
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy. mattia.stucchi@unimi.it.
authors.forename: Alessandra
authors.identifier: http://orcid.org/0000-0002-0397-2636
authors.initials: A
authors.lastname: Silvani
mesh_terms: D056945:Hep G2 Cells; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008958:Models, Molecular; D057786:Peptidomimetics / Q000737:chemistry* / Q000494:pharmacology*; D000071449:Proprotein Convertase 9 / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D011973:Receptors, LDL / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D057786:Peptidomimetics; D011973:Receptors, LDL; C029899:imidazole; D000071449:Proprotein Convertase 9