Targeting RNA with small molecules: from fundamental principles towards the clinic

Falese, James P.; Donlic, Anita; Hargrove, Amanda E.

doi:10.1039/d0cs01261k

Cited by 138 publications

(138 citation statements)

References 55 publications

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“…It's reported that RNA-targeted fluorescent probes commonly consist of aromatic rings, nitrogen heterocyclic rings and amine groups. 34,35 Phenylenediamines are commonly used precursors for preparing CDs to provide heterocyclic compounds and polymers. According to previous reports, CDs prepared by m-PD have potential in targeting nucleolar RNA.…”

Section: Fabrication and Characterization Of Rna-cdsmentioning

confidence: 99%

A Carbonized Fluorescent Nucleolus Probe Discloses RNA Reduction in the Process of Mitophagy

et al. 2022

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Mitophagy is a complicated process of cell metabolism that exhibits dynamic spatiotemporal coordination between multiple organelles. Despite its relevance to nucleoli, visualizing the distribution of nucleolar RNA in the process of mitophagy remains a great challenge because of the difficulty in specifically labelling RNA.Herein, we demonstrate a robust carbonized fluorescent probe with folic acid (FA) and m-phenylenediamine (m-PD) as the precursors, which displays superior RNA-anchoring ability and fast cellular permeability to tag nucleolar RNA in living cells. More importantly, this probe possesses spontaneous blinking behavior in physiological conditions, which is suitable for nanoscopic imaging of subtle changes in the distribution of nucleolar RNA. Overall, this work presents a new way for in situ observation of nanoscopic behavior of nucleolar RNA in living cells, providing a powerful approach for further exploration of cellular metabolism in mitophagy.

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Section: Fabrication and Characterization Of Rna-cdsmentioning

confidence: 99%

A Carbonized Fluorescent Nucleolus Probe Discloses RNA Reduction in the Process of Mitophagy

et al. 2022

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“…RNA targets that expand druggable genome, including those linked to ‘undruggable’ protein targets or non-coding microRNAs, are of particular interest ( 5 ). However, RNA drug development is dotted with numerous obstacles ( 6 ), among others, related to the low chemical diversity and the dynamic nature of RNA structures. Similar to proteins, RNA molecules are highly structured to form binding sites, through which small molecules can modulate them ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Structure-based deep learning for binding site detection in nucleic acid macromolecules

Kozlovskii

Popov

2021

NAR Genomics and Bioinformatics

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Structure-based drug design (SBDD) targeting nucleic acid macromolecules, particularly RNA, is a gaining momentum research direction that already resulted in several FDA-approved compounds. Similar to proteins, one of the critical components in SBDD for RNA is the correct identification of the binding sites for putative drug candidates. RNAs share a common structural organization that, together with the dynamic nature of these molecules, makes it challenging to recognize binding sites for small molecules. Moreover, there is a need for structure-based approaches, as sequence information only does not consider conformation plasticity of nucleic acid macromolecules. Deep learning holds a great promise to resolve binding site detection problem, but requires a large amount of structural data, which is very limited for nucleic acids, compared to proteins. In this study we composed a set of ∼2000 nucleic acid-small molecule structures comprising ∼2500 binding sites, which is ∼40-times larger than previously used one, and demonstrated the first structure-based deep learning approach, BiteNetN, to detect binding sites in nucleic acid structures. BiteNetN operates with arbitrary nucleic acid complexes, shows the state-of-the-art performance, and can be helpful in the analysis of different conformations and mutant variants, as we demonstrated for HIV-1 TAR RNA and ATP-aptamer case studies.

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“…13 The rapidly increasing amount of publications on RNA-targeting molecules points out the emerging importance of this interdisciplinary research area. [14][15][16][17][18][19] Similar to DNA and proteins, RNA possesses a range of important features as a drug target. Like DNA, the chemical building units of RNA are fewer and less complex in comparison to those of proteins.…”

Section: Introductionmentioning

confidence: 99%

Photoswitches for controllable RNA binding: a future approach in the RNA-targeting therapy

Berdnikova

2021

Chem. Commun.

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Targeting RNA with small molecules: from fundamental principles towards the clinic

Abstract: This tutorial review describes the fundamental principles and recent advances in developing small molecule-based therapeutics for disease-associated RNAs.

Cited by 138 publications

References 55 publications

A Carbonized Fluorescent Nucleolus Probe Discloses RNA Reduction in the Process of Mitophagy

A Carbonized Fluorescent Nucleolus Probe Discloses RNA Reduction in the Process of Mitophagy

Structure-based deep learning for binding site detection in nucleic acid macromolecules

Photoswitches for controllable RNA binding: a future approach in the RNA-targeting therapy

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