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Programming Fluorogenic DNA Probes for Rapid Detection of Steroids
Author(s) -
Ebrahimi Sasha B.,
Samanta Devleena,
Partridge Benjamin E.,
Kusmierz Caroline D.,
Cheng Ho Fung,
Grigorescu Arabela A.,
Chávez Jorge L.,
Mirau Peter A.,
Mirkin Chad A.
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202103440
Subject(s) - aptamer , chemistry , intercalation (chemistry) , molecular recognition , fluorescence , biosensor , dna , nanotechnology , combinatorial chemistry , biophysics , computational biology , molecule , biochemistry , microbiology and biotechnology , materials science , biology , physics , inorganic chemistry , organic chemistry , quantum mechanics
The ability of aptamers to recognize a variety of different molecules has fueled their emergence as recognition agents to probe complex media and cells. Many detection strategies require aptamer binding to its target to result in a dramatic change in structure, typically from an unfolded to a folded state. Here, we report a strategy based on forced intercalation (FIT) that increases the scope of aptamer recognition by transducing subtle changes in aptamer structures into fluorescent readouts. By screening a library of green‐fluorescent FIT‐aptamers whose design is guided by computational modeling, we could identify hits that sense steroids like dehydroepiandrosterone sulfate (DHEAS) down to 1.3 μM with no loss in binding affinity compared to the unmodified aptamer. This enabled us to study DHEAS in clinical serum samples with several advantages over gold standard methods, including rapid readout (<30 min), simple instrumentation (plate‐reader), and low sample volumes (10 μL).