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Updated: Aug 18, 2026

A Method for Selecting Structure-switching Aptamers Applied to a Colorimetric Gold Nanoparticle Assay
Published on: February 28, 2015
Selection of optimised ligands by fluorescence-activated bead sorting
Alexandra R Paul1, Mario Falsaperna1, Helen Lavender2
1School of Chemistry and Forensic Sciences, Division of Natural Sciences, University of Kent Canterbury CT2 7NH UK.
Abstract:
The chemistry of aptamers is largely limited to natural nucleotides, and although modifications of nucleic acids can enhance target aptamer affinity, there has not yet been a technology for selecting the right modifications in the right locations out of the vast number of possibilities, because enzymatic amplification does not transmit sequence-specific modification information. Here we show the first method for the selection of specific nucleoside modifications that increase aptamer binding efficacy, using the oncoprotein EGFR as a model target. Using fluorescence-activated bead sorting (FABS), we have successfully selected optimized aptamers from a library of >65 000 variations. Hits were identified by tandem mass spectrometry and validated by using an EGFR binding assay and computational docking studies. Our results provide proof of concept for this novel strategy for the selection of chemically optimised aptamers and offer a new method for rapidly synthesising and screening large aptamer libraries to accelerate diagnostic and drug discovery.
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