Synthetic Peptides: Promising Modalities for the Targeting of Disease‐Related Nucleic Acids

Nucleic acids play pivotal roles in life processes. Their dysregulation is implicated in numerous diseases while therapeutic compounds targeting them remain limited. In this review we focus on synthetic peptides which offer potential solutions for targeting double-stranded DNA, regulatory G-quadruplexes and non-coding RNAs.

Abstract

DNA and RNA play pivotal roles in life processes by storing and transferring genetic information, modulating gene expression, and contributing to essential cellular machinery such as ribosomes. Dysregulation and mutations in nucleic acid-related processes are implicated in numerous diseases. Despite the critical impact on health of nucleic acid mutations or dysregulation, therapeutic compounds addressing these biomolecules remain limited. Peptides have emerged as a promising class of molecules for biomedical research, offering potential solutions for challenging drug targets. This review focuses on the use of synthetic peptides to target disease-related nucleic acids. We discuss examples of peptides targeting double-stranded DNA, including the clinical candidate Omomyc, and compounds designed for regulatory G-quadruplexes. Further, we provide insights into both library-based screenings and the rational design of peptides to target regulatory human RNA scaffolds and viral RNAs, emphasizing the potential of peptides in addressing nucleic acid-related diseases.

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