Paris, France - A new research study published in Nature Communications highlights how Depixus’ scalable single molecule technology can provide detailed mechanistic insights into RNA-ligand binding, supporting the development of novel therapeutics.

Based on magnetic force spectroscopy (MFS), Depixus’ large scale interactomics platform is the first analytical technology capable of exploring dynamic biomolecular interactions both in real time and from thousands of individual molecules in parallel.

The study was led by Dr. John “Jay” Schneekloth, Jr. a leading expert in RNA-targeted drug discovery at the National Cancer Institute, part of the US National Institutes of Health. Depixus’ scalable MFS platform was used to probe the interactions between the Bacillus subtilis (Bsu) PreQ1 bacterial riboswitch and either its natural ligand (PreQ1) or a synthetic small molecule known as Compound 4.

Riboswitches are structured sequences of RNA commonly found in the 5′ untranslated regions of bacterial mRNAs that help to control metabolic pathways. Ligands such as metabolites bind to the riboswitch, inducing a conformational change in the secondary structure and altering gene expression. This makes them an attractive group of novel antibacterial drug targets.

In a key part of the study, Depixus’ MFS platform was used to precisely measure the effects of either PreQ1 or Compound 4 binding on immobilized target riboswitch RNA aptamers. The results showed both ligands stabilized the RNA structure, and the effect of compound concentration was measured.

Importantly, analysis of MFS data streams coming from individual interactions revealed that the two ligands had very distinct modes of action - a distinction that would have been missed using other analytical techniques that only generate surrogate or bulk, averaged measurements.

Jimmy Ouellet, Chief Scientist at Depixus, said “This study highlights how our ability to carry out independent analysis of individual biomolecular interactions enables us to visualize RNA-ligand interactions in real time, gathering valuable insights into distinct mechanisms of action. With our large-scale MFS platform we now have a technology that can see biology as it really happens, exploring the mechanistic impact of compounds on their targets at the level of individual molecules, generating detailed information about binding kinetics and more.”

Depixus’ unique platform delivers valuable data about a wide range of individual dynamic molecular interactions - including between RNA, DNA, proteins and small molecules - decoding disease mechanisms and unlocking faster routes to more effective therapies. Find out more at http://www.depixus.com/

Reference: Parmar S, et al. Nat Commun. (2024) 15:8173. https://www.nature.com/articles/s41467-024-52235-3