Exploring the Landscape of Aptamers: From Cross-Reactive to Selective to Specific, High-Affinity Receptors for Cocaine.

Autor:	Yang K; Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Alkhamis O; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., Canoura J; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., Bryant A; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., Gong EM; Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Barbu M; Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Taylor S; Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Nikic D; Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Banerjee S; Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Xiao Y; Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., Stojanovic MN; Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States.; Departments of Biomedical Engineering and Systems Biology, Columbia University, New York, New York 10032, United States., Landry DW; Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States.
Jazyk:	angličtina
Zdroj:	JACS Au [JACS Au] 2024 Feb 13; Vol. 4 (2), pp. 760-770. Date of Electronic Publication: 2024 Feb 13 (Print Publication: 2024).
DOI:	10.1021/jacsau.3c00781
Abstrakt:	We reported over 20 years ago MNS-4.1, the first DNA aptamer with a micromolar affinity for cocaine. MNS-4.1 is based on a structural motif that is very common in any random pool of oligonucleotides, and it is actually a nonspecific hydrophobic receptor with wide cross-reactivity with alkaloids and steroids. Despite such weaknesses preventing broad applications, this aptamer became widely used in proof-of-concept demonstrations of new formats of biosensors. We now report a series of progressively improved DNA aptamers recognizing cocaine, with the final optimized receptors having low nanomolar affinity and over a thousand-fold selectivity over the initial cross-reactants. In the process of optimization, we tested different methods to eliminate cross-reactivities and improve affinity, eventually achieving properties that are comparable to those of the reported monoclonal antibody candidates for the therapy of overdose. Multiple aptamers that we now report share structural motifs with the previously reported receptor for serotonin. Further mutagenesis studies revealed a palindromic, highly adaptable, broadly cross-reactive hydrophobic motif that could be rebuilt through mutagenesis, expansion of linker regions, and selections into receptors with exceptional affinities and varying specificities. Competing Interests: The authors declare no competing financial interest. (© 2024 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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