Small Molecules Targeting the miRNA-Binding Domain of Argonaute 2: From Computer-Aided Molecular Design to RNA Immunoprecipitation.

Teresa Bellissimo, Silvia Masciarelli, Elena Poser, Ilaria Genovese, Alberto Del Rio, Gianni Colotti, Francesco Fazi

Journal: Methods in molecular biology (Clifton, N.J.) 2018;1517():211-221

PMID: 27924485

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.

Address: Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161, Rome, Italy.; Pathology, Italian National Research Council, Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, 00161, Rome, Italy.; CNR-National Research Council of Italy, Institute for Organic Chemistry and Photoreactivity, Via P. Gobetti 101, 40129, Bologna, Italy. [email protected].; Innovamol Srls, Viale A. Corassori 24, 41124, Modena, Italy. [email protected].; Pathology, Italian National Research Council, Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, 00161, Rome, Italy. [email protected].; Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161, Rome, Italy. [email protected].

DOI: 10.1007/978-1-4939-6563-2_15

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MeSH Terms: Argonaute Proteins, Cell Differentiation, Drug Delivery Systems, Gene Expression Regulation, Leukemic, Humans, Immunoprecipitation, Leukemia, MicroRNAs, Models, Molecular, Small Molecule Libraries, Tretinoin