Small Molecules

Small Molecule Targeting

Detecting small molecules remains a significant challenge in the life sciences because of a lack of reliable reagents and assays.

Aptamer Group developed an adapted displacement approach that not only improves selection results but also facilitates better assay design and execution.

The binding of our small molecule-targeting aptamers (and Optimers™) relies on a conformational change, which may be exploited in a number of assay formats; including ELISA-like assays, Biosensors, Molecular Beacons and Lateral Flow Devices.

Aptamers selected against small molecules without modifications to target and in assay matrix

Selecting aptamers to small molecule targets is challenging. Immobilising small molecules can change chemical characteristics and sterically hinder aptamer interactions. Aptamer Group use a unique displacement method to address these issues. We select against molecules in solution and in biologically relevant conditions.

Our fully automated approach uses  an immobilised aptamer library while  the small molecule target is kept in solution. Weakly bound or non-specifically displaced sequences are removed in a series of washes, target specific binders are displaced and recovered.
In this example, aptamers were selected to bind with high specificity for one antibiotic but not bind a closely related drug. Counter selection steps with plasma were included to ensure functionality of the generated aptamers in future diagnostic tests.
Small molecule displacement aptamers are readily integrated into ELISA-like assays. Measurements in buffered plasma show that the generated aptamer gives a clear concentration-dependent  binding signal for its target (green)  while  the structurally closely related counter target is only recognised at highest concentration (red).