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A Method for Selecting Structure-switching Aptamers Applied to a Colorimetric Gold Nanoparticle Assay

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Click Capture SELEX for the Identification of Click-Modified Aptamers Targeting Small Molecules in Solution.

Philipp Menke¹, Carmelo Di Primo², Felix Bernhardt¹

¹Life and Medical Science Institute (LIMES), University of Bonn, Bonn, Germany.

Chemistry (Weinheim an Der Bergstrasse, Germany)

|April 4, 2026

Summary

This study introduces click capture SELEX, a novel method for discovering chemically modified aptamers (clickmers) that bind small molecules. This technique expands the chemical diversity of aptamers for improved molecular recognition.

Keywords:

CuAAC SELEX aptamer method development nucleobase modifications

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Area of Science:

Biochemistry
Molecular Biology
Chemical Biology

Background:

Aptamers are nucleic acid-based ligands that bind targets through supramolecular interactions.
Canonical nucleobases limit the chemical diversity and interaction properties of aptamers.
Nucleobase modifications can expand the capabilities of aptamer-target interactions.

Purpose of the Study:

To develop an improved SELEX method for identifying chemically modified aptamers (clickmers).
To enrich aptamers with enhanced binding capabilities to small molecules.
To demonstrate the utility of click capture SELEX for small molecule aptamer discovery.

Main Methods:

Developed click capture SELEX, a method for selecting chemically modified aptamers.
Utilized an indole-modified DNA library for aptamer selection.
Applied the method to identify aptamers that specifically bind kanamycin A.

Main Results:

Successfully identified indole-modified DNA clickmers that specifically bind kanamycin A.
Demonstrated the efficacy of click capture SELEX in selecting aptamers against small molecules in solution.
Validated the adaptability of the method for various small molecule targets.

Conclusions:

Click capture SELEX overcomes limitations of traditional SELEX, particularly with immobilized targets.
The method enables the discovery of aptamers with expanded chemical diversity.
This approach is broadly applicable for identifying aptamers against diverse small molecules.