title: Small Molecules Targeting the miRNA-Binding Domain of Argonaute 2: From Computer-Aided Molecular Design to RNA Immunoprecipitation.
abstract: The development of small-molecule-based target therapy design for human disease and cancer is object of growing attention. Recently, specific microRNA (miRNA) mimicking compounds able to bind the miRNA-binding domain of Argonaute 2 protein (AGO2) to inhibit miRNA loading and its functional activity were described. Computer-aided molecular design techniques and RNA immunoprecipitation represent suitable approaches to identify and experimentally determine if a compound is able to impair the loading of miRNAs on AGO2 protein. Here, we describe these two methodologies that we recently used to select a specific compound able to interfere with the AGO2 functional activity and able to improve the retinoic acid-dependent myeloid differentiation of leukemic cells.
authors.affiliation: Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161, Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Bellissimo
authors.affiliation: Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Masciarelli
authors.affiliation: Pathology, Italian National Research Council, Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, 00161, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Poser
authors.affiliation: Pathology, Italian National Research Council, Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, 00161, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Genovese
authors.affiliation: CNR-National Research Council of Italy, Institute for Organic Chemistry and Photoreactivity, Via P. Gobetti 101, 40129, Bologna, Italy. alberto.delrio@isof.cnr.it.|Innovamol Srls, Viale A. Corassori 24, 41124, Modena, Italy. alberto.delrio@isof.cnr.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Del Rio
authors.affiliation: Pathology, Italian National Research Council, Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, 00161, Rome, Italy. gianni.colotti@uniroma1.it.
authors.forename: Gianni
authors.initials: G
authors.lastname: Colotti
authors.affiliation: Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161, Rome, Italy. francesco.fazi@uniroma1.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fazi
mesh_terms: D060565:Argonaute Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods*; D007938:Leukemia / Q000235:genetics / Q000628:therapy*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D008958:Models, Molecular; D054852:Small Molecule Libraries / Q000737:chemistry / Q000627:therapeutic use; D014212:Tretinoin / Q000494:pharmacology
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D035683:MicroRNAs; D054852:Small Molecule Libraries; D014212:Tretinoin
keywords: Argonaute 2; Molecular docking techniques; Myeloid differentiation; RNA immunoprecipitation; Small molecules; microRNAs