title: Recognition and sensing of low-epitope targets via ternary complexes with oligonucleotides and synthetic receptors.
abstract: 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.
authors.affiliation: Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York 10032, USA.
authors.forename: Kyung-Ae
authors.initials: KA
authors.lastname: Yang
authors.affiliation: Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York 10032, USA.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Barbu
authors.affiliation: Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York 10032, USA.
authors.forename: Marlin
authors.initials: M
authors.lastname: Halim
authors.affiliation: Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York 10032, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Pallavi
authors.affiliation: Department of Pathology, Columbia University, New York, New York 10032, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kim
authors.affiliation: Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York 10032, USA.
authors.forename: Dmitry M
authors.initials: DM
authors.lastname: Kolpashchikov
authors.affiliation: Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York 10032, USA.
authors.forename: Stevan
authors.initials: S
authors.lastname: Pecic
authors.affiliation: Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York 10032, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Taylor
authors.affiliation: Department of Pathology, Columbia University, New York, New York 10032, USA.
authors.forename: Tilla S
authors.initials: TS
authors.lastname: Worgall
authors.affiliation: 1] Division of Experimental Therapeutics, Department of Medicine, Columbia University, New York, New York 10032, USA [2] Departments of Biomedical Engineering and Systems Biology, Columbia University, New York, New York 10032, USA.
authors.forename: Milan N
authors.initials: MN
authors.lastname: Stojanovic
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism; D001897:Boronic Acids / Q000737:chemistry; D056831:Coordination Complexes / Q000097:blood; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000032:analysis / Q000737:chemistry; D006801:Humans; D009005:Monosaccharides / Q000737:chemistry / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry*; D010649:Phenylalanine / Q000032:analysis / Q000097:blood; D062165:Receptors, Artificial / Q000737:chemistry* / Q000378:metabolism; D012238:Rhodium / Q000737:chemistry
chemical_list: D052157:Aptamers, Nucleotide; D001897:Boronic Acids; D056831:Coordination Complexes; D000939:Epitopes; D009005:Monosaccharides; D009841:Oligonucleotides; D062165:Receptors, Artificial; D010649:Phenylalanine; D012238:Rhodium; D005947:Glucose