Maria Duca

Design of novel RNA ligands that bind stem–bulge HIV-1 TAR RNA

We report here the rational design and the synthesis of a new series of RNA ligands. These molecules are constituted of various binding motifs that interact cooperatively with HIV-1 TAR RNA, used as a model.

Fluorescent labeling of human mesenchymal stem cells by thiophene fluorophores conjugated to a lipophilic carrier

Fluorescent labeling of human mesenchymal stem cells (hMSCs) is essential for their study in vitro and in vivo. Here, we report a new chemical biodelivery method for labeling hMSCs using a series of very efficient and highly versatile thiophene-based fluorescent dyes. Such conjugates contribute to a stable and viable labeling of hMSCs and constitute a promising strategy for in vivo applications.

Oncogenic MicroRNAs Biogenesis as a Drug Target: Structure–Activity Relationship Studies on New Aminoglycoside Conjugates

MicroRNAs (miRNAs) are a recently discovered category of small RNA molecules that regulate gene expression at the post-transcriptional level. Accumulating evidence indicates that miRNAs are aberrantly expressed in a variety of human cancers and that the inhibition of these oncogenic miRNAs could find application in the therapy of different types of cancer. Herein, we describe the synthesis and biological evaluation of new small-molecule drugs that target oncogenic miRNAs production. In particular, we chose to target two miRNAs (i.e., miRNA-372 and -373) implicated in various types of cancer, such as gastric cancer. Their precursors (pre-miRNAs) are overexpressed in cancer cells and lead to mature miRNAs after cleavage of their stem-loop structure by the enzyme Dicer in the cytoplasm. Some of the newly synthesized conjugates can inhibit Dicer processing of the targeted pre-miRNAs in vitro with increased efficacy relative to our previous results (D.D. Vo et al., ACS Chem. Biol. 2014, 9, 711-721) and, more importantly, to inhibit proliferations of adenocarcinoma gastric cancer (AGS) cells overexpressing these miRNAs, thus representing promising leads for future drug development.

Small-molecule approaches toward the targeting of oncogenic miRNAs: roadmap for the discovery of RNA modulators

miRNAs are a recently discovered class of small noncoding RNAs implicated in the regulation of gene expression. The deregulation of miRNAs levels has been linked to the development of various cancers where oncogenic miRNAs are overexpressed and tumor suppressor miRNAs are underexpressed. Here we report the three main strategies developed in order to discover small-molecule drugs able to selectively interfere with oncogenic miRNAs: the high throughput screening of large libraries of compounds, the focused screening of small libraries of molecules that are known to be able to interact with RNA thus being supposed modulators of miRNAs pathway and the design of small molecules based on the secondary structure of targeted RNA and/or three-dimensional structure of enzymes involved in miRNAs pathway.

Design of Multimodal Small Molecules Targeting miRNAs Biogenesis: Synthesis and In Vitro Evaluation

microRNAs (miRNAs) are emerging as novel biological targets for medicinal chemists to develop chemical tools for intracellular regulation. In this context, the discovery of small-molecule drugs targeting specific miRNAs and modulating their production or function represents a very promising approach that could be further developed for targeted therapy in miRNA-related pathologies. Here, we describe the design of multimodal small molecules as RNA ligands targeting DICER-mediated miRNA maturation. The synthesis and the biochemical evaluation as ligands of stem-loop-structured precursor microRNAs (pre-miRNAs) are reported.