Journal
NATURE CHEMISTRY
Volume 6, Issue 11, Pages 1003-1008Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEM.2058
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Funding
- National Science Foundation [CBET-1033288, CBET-1026592]
- National Institutes of Health [RGM104960]
- Juvenile Diabetes Research Foundation (Innovative Program)
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1033288] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1026592] Funding Source: National Science Foundation
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Oligonucleotide-based receptors or aptamers can interact with small molecules, but the ability to achieve high-affinity and specificity of these interactions depends strongly on functional groups or epitopes displayed by the binding targets. Some classes of targets are particularly challenging: for example, monosaccharides have scarce functionalities and no aptamers have been reported to recognize, let alone distinguish from each other, glucose and other hexoses. Here we report aptamers that differentiate low-epitope targets such as glucose, fructose or galactose by forming ternary complexes with high-epitope organic receptors for monosaccharides. In a follow-up example, we expand this method to isolate high-affinity oligonucleotides against aromatic amino acids complexed in situ with a nonspecific organometallic receptor. The method is general and enables broad clinical use of aptamers for the detection of small molecules in mix-and-measure assays, as demonstrated by monitoring postprandial waves of phenylalanine in human subjects.
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