Specificity and ligand affinities of the cocaine aptamer: impact of structural features and physiological NaCl

dc.contributor.author Nilsen-Hamilton, Marit
dc.contributor.author Sachan, Ashish
dc.contributor.author Ilgu, Muslum
dc.contributor.author Kempema, Aaron
dc.contributor.author Kraus, George
dc.contributor.author Kraus, George
dc.contributor.author Nilsen-Hamilton, Marit
dc.contributor.department Biochemistry, Biophysics and Molecular Biology
dc.contributor.department Chemistry
dc.date 2018-02-18T22:12:47.000
dc.date.accessioned 2020-06-30T01:24:27Z
dc.date.available 2020-06-30T01:24:27Z
dc.date.copyright Fri Jan 01 00:00:00 UTC 2016
dc.date.issued 2016-06-27
dc.description.abstract <p>The cocaine aptamer has been seen as a good candidate for development as a probe for cocaine in many contexts. Here, we demonstrate that the aptamer binds cocaine, norcocaine, and cocaethylene with similar affinities and aminoglycosides with similar or higher affinities in a mutually exclusive manner with cocaine. Analysis of its affinities for a series of cocaine derivatives shows that the aptamer specificity is the consequence of its interaction with all faces of the cocaine molecule. Circular dichroism spectroscopy and 2-aminopurine (2AP) fluorescence studies show no evidence of large structural rearrangement of the cocaine aptamer upon ligand binding, which is contrary to the general view of this aptamer. The aptamer’s affinity for cocaine and neomycin-B decreases with the inclusion of physiological NaCl. The substitution of 2AP for A in position 6 (2AP6) of the aptamer sequence eliminated the effect of NaCl on its affinities for cocaine and analogues, but not for neomycin-B, showing a selective effect of 2AP substitution on cocaine binding. The affinity for cocaine also decreased with increasing concentrations of serum or urine, with the 2AP6 substitution blunting the effect of urine. Its low affinities for cocaine and metabolites and its ability to bind irrelevant compounds limit the opportunities for application of this aptamer in its current form as a selective and reliable sensor for cocaine. However, these studies also show that a small structural adjustment to the aptamer (2AP exchanged for adenine) can increase its specificity for cocaine in physiological NaCl relative to an off-target ligand.</p>
dc.description.comments <p>This is an article from Sachan, Ashish, Muslum Ilgu, Aaron Kempema, George A. Kraus, and Marit Nilsen-Hamilton. "Specificity and ligand affinities of the cocaine aptamer: impact of structural features and physiological NaCl." Analytical chemistry 88, no. 15 (2016): 7715-7723. DOI:<a href="http://dx.doi.org/10.1021/acs.analchem.6b01633" target="_blank" title="Specificity and Ligand Affinities of the Cocaine Aptamer: Impact of Structural Features and Physiological NaCl"> 10.1021/acs.analchem.6b01633</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/chem_pubs/991/
dc.identifier.articleid 1993
dc.identifier.contextkey 10683255
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath chem_pubs/991
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/15495
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/chem_pubs/991/0-2016_Kraus_SpecifictyLigand_ACSLicense.pdf|||Sat Jan 15 02:39:29 UTC 2022
dc.source.bitstream archive/lib.dr.iastate.edu/chem_pubs/991/2016_Kraus_SpeficityLigand.pdf|||Sat Jan 15 02:39:30 UTC 2022
dc.source.uri 10.1021/acs.analchem.6b01633
dc.subject.disciplines Biochemistry, Biophysics, and Structural Biology
dc.subject.disciplines Chemistry
dc.title Specificity and ligand affinities of the cocaine aptamer: impact of structural features and physiological NaCl
dc.type article
dc.type.genre article
dspace.entity.type Publication
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