Targeting Ribonucleases with Small Molecules and Bifunctional Molecules.

Area of Science:

• Biochemistry
• Molecular Biology
• Chemical Biology

Background:

• Ribonucleases (RNases) are crucial enzymes that cleave and process RNA molecules.
• RNase activity regulates RNA biogenesis, metabolism, and degradation, impacting cellular functions.
• RNases are validated therapeutic targets for various diseases, including infections, autoimmune disorders, and cancer.

Purpose of the Study:

• To summarize the discovery of small-molecule inhibitors and activators targeting bacterial, viral, and human RNases.
• To highlight emerging bifunctional molecules that leverage chemically induced proximity for RNase-based RNA manipulation.
• To discuss current trends and future prospects in developing RNase-targeting molecules for biological and therapeutic applications.

Main Methods:

• Literature review of small-molecule discovery efforts targeting RNases.
• Analysis of recent advances in chemically induced proximity strategies for RNase modulation.
• Synthesis and characterization of bifunctional molecules designed for RNase-mediated RNA degradation or processing inhibition.

Main Results:

• Numerous small-molecule inhibitors and activators for various RNases have been identified.
• Bifunctional molecules demonstrate novel mechanisms for precise RNA targeting and degradation.
• Emerging strategies show promise for developing targeted therapies against diseases driven by aberrant RNA metabolism.

Conclusions:

• Small molecules targeting RNases represent a promising avenue for therapeutic intervention.
• Bifunctional molecules offer enhanced specificity and efficacy in modulating RNA biology.
• Continued development of RNase-targeting agents holds significant potential for diverse clinical applications.