Tuberactinomycin antibiotics: Biosynthesis, anti-mycobacterial action, and mechanisms of resistance

Laughlin, Zane T.; Conn, Graeme L.

doi:10.3389/fmicb.2022.961921

Environment‐Responsive Peptide Dimers Bind and Stabilize Double‐Stranded RNA

McLoughlin,

Albers,

Collado Camps

et al. 2023

Angewandte Chemie

0

View full text Add to dashboard Cite

Double‐stranded RNAs (dsRNA) possess immense potential for biomedical applications. However, their therapeutic utility is limited by low stability and poor cellular uptake. Different strategies have been explored to enhance the stability of dsRNA, including the incorporation of modified nucleotides, and the use of diverse carrier systems. Nevertheless, these have not resulted in a broadly applicable approach thereby preventing the wide‐spread application of dsRNA for therapeutic purposes. Herein, we report the design of dimeric stapled peptides based on the RNA‐binding protein TAV2b. These dimers are obtained via disulfide formation and mimic the natural TAV2b assembly. They bind and stabilize dsRNA in the presence of serum, protecting it from degradation. In addition, peptide binding also promotes cellular uptake of dsRNA. Importantly, peptide dimers monomerize under reducing conditions which results in a loss of RNA binding. These findings highlight the potential of peptide‐based RNA binders for the stabilization and protection of dsRNA, representing an appealing strategy towards the environment‐triggered release of RNA. This can broaden the applicability of dsRNA, such as short interfering RNAs (siRNA), for therapeutic applications.

show abstract

Environment‐Responsive Peptide Dimers Bind and Stabilize Double‐Stranded RNA

McLoughlin,

Albers,

Collado Camps

et al. 2023

View full text Add to dashboard Cite

Double‐stranded RNAs (dsRNA) possess immense potential for biomedical applications. However, their therapeutic utility is limited by low stability and poor cellular uptake. Different strategies have been explored to enhance the stability of dsRNA, including the incorporation of modified nucleotides, and the use of diverse carrier systems. Nevertheless, these have not resulted in a broadly applicable approach thereby preventing the wide‐spread application of dsRNA for therapeutic purposes. Herein, we report the design of dimeric stapled peptides based on the RNA‐binding protein TAV2b. These dimers are obtained via disulfide formation and mimic the natural TAV2b assembly. They bind and stabilize dsRNA in the presence of serum, protecting it from degradation. In addition, peptide binding also promotes cellular uptake of dsRNA. Importantly, peptide dimers monomerize under reducing conditions which results in a loss of RNA binding. These findings highlight the potential of peptide‐based RNA binders for the stabilization and protection of dsRNA, representing an appealing strategy towards the environment‐triggered release of RNA. This can broaden the applicability of dsRNA, such as short interfering RNAs (siRNA), for therapeutic applications.

show abstract