UK scientists have developed a hydrogel slide for monitoring interactions between small molecules and proteins. The slide is an improvement on commercially available slides and could improve drug discovery, they claim.

The 3D hydrogel-coated slide can be used as a small-molecule microarray

Microarrays are used for high throughput studies of molecular interactions. For example, scientists have immobilised small molecules as spots on 2D slides then probed them with a fluorescently labelled target protein to try to find new drug candidates. But detecting the fluorescent signals is difficult because the interactions are weak and only a small number of molecules can be attached to the slides.

Now David Spring, at the University of Cambridge, and colleagues have made a 3D slide by covering a glass slide with a polyethylene glycol-based hydrogel. Because the 3D slide has a greater surface area than previous 2D slides, more small molecules can be attached to the hydrogel surface.

Spring compared his slide with a commercially available 3D polymer-coated slide. He functionalised both slides with biotin and used fluorescently labelled avidin as the probe protein. The hydrogel slide had a loading capacity an order of magnitude greater than the polymer slide and showed on average a six-fold higher fluorescent intensity.

'This is a valuable achievement that confers several significant advantages, including improved signal-to-noise and enhanced sensitivity, especially when screening for low abundant protein targets,' comments Mahesh Uttamchandani, an expert in small molecule microarrays at DSO National Laboratories in Singapore.

Spring says the surface of the hydrogel slide could be modified in future to incorporate other functional groups. This would enable targeting of different molecule-protein interactions and so widen the chemical toolbox available to the researcher.

Most importantly, adds Spring, the improved signal detection will help emphasise the importance of using small molecule arrays for drug discovery. But he acknowledges that the next big challenge will be 'convincing the pharmaceutical industry that this is a robust and cost-effective way of discovering new drugs'.

Emma Shiells

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