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Selection of optimised ligands by fluorescence-activated bead sorting

Paul, Alexandra. R, Falsaperna, Mario, Lavender, Helen, Garrett, Michelle D., Serpell, Christopher J. (2023) Selection of optimised ligands by fluorescence-activated bead sorting. Chemical Science, 14 (35). pp. 9517-9525. ISSN 2041-6520. E-ISSN 2041-6539. (doi:10.1039/d3sc03581f) (KAR id:102640)


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.

Item Type: Article
DOI/Identification number: 10.1039/d3sc03581f
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Divisions > Division of Natural Sciences > Chemistry and Forensics
Funders: University of Kent (
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 18 Oct 2023 11:55 UTC
Last Modified: 09 Jan 2024 11:59 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Garrett, Michelle D..

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Serpell, Christopher J..

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