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- W4366318087 abstract "Ribonucleic acid (RNA) is a key regulator of many biological processes including translation, gene expression, gene splicing, developmental timing, and catalysis and thus is an attractive target for potential therapeutics. The two methods most widely used to target RNA are antisense oligonucleotides (ASOs) and small molecules interacting with RNAs (SMIRNAs). While ASOs have demonstrated success in targeting unstructured regions of RNA by sequence complementarity, SMIRNAs target unique structural folds within an RNA through hydrogen bonding, stacking (electrostatic), and van der Waals interactions. As structural features of RNAs can accurately be predicted by in silico methods, the identification of SMIRNAs that can target structures in RNAs that cause or contribute to disease represents an attractive route for therapeutic intervention. In this review, we discuss current methodologies for the facile identification of SMIRNAs informed by RNA sequence. We also cover the modulation of various classes of RNA by SMIRNAs including microRNAs (miRNAs), messenger RNAs (mRNAs), and long non-coding RNAs (lncRNAs) among others. Further, the studies discussed herein demonstrate how SMIRNAs can be lead-optimized to enhance desirable features such as low molecular weight, good bioavailability, and increased potency and selectivity. Importantly, various strategies have been implemented that augment the functionality of SMIRNAs, converting their modes of action from simple binding to effecting cleavage. While the field of SMIRNAs is still in its early stages compared to proteins, the fundamental principles to design SMIRNAs described here provide a roadmap for the rapid identification of molecules available for chemical biology and therapeutic advancement." @default.
- W4366318087 created "2023-04-20" @default.
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- W4366318087 creator A5050381474 @default.
- W4366318087 date "2023-01-01" @default.
- W4366318087 modified "2023-09-26" @default.
- W4366318087 title "Targeting RNA with Small Molecules" @default.
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- W4366318087 doi "https://doi.org/10.1007/978-981-16-1313-5_96-1" @default.
- W4366318087 hasPublicationYear "2023" @default.
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