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Rational Design of a Redox‐Labeled Chiral Target for an Enantioselective Aptamer‐Based Electrochemical Binding Assay
Author(s) -
Moreau Julie,
Challier Lylian,
Lalaoui Noémie,
Mavré François,
Noël Vincent,
Limoges Benoît,
Schöllhorn Bernd,
Fave Claire
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201302979
Subject(s) - enantiomer , chemistry , enantioselective synthesis , aptamer , redox , combinatorial chemistry , dissociation constant , dissociation (chemistry) , cyclic voltammetry , molecule , electrochemistry , enantiomeric excess , ligand (biochemistry) , stereochemistry , electrode , organic chemistry , catalysis , biochemistry , receptor , biology , genetics
A series of redox‐labeled L ‐tyrosinamide ( L ‐Tym) derivatives was prepared and the nature of the functional group and the chain length of the spacer were systematically varied in a step‐by‐step affinity optimization process of the tracer for the L ‐Tym aptamer. The choice of the labeling position on L ‐Tym proved to be crucial for the molecular recognition event, which could be monitored by cyclic voltammetry and is based on the different diffusion rates of free and bound targets in solution. From this screening approach an efficient electroactive tracer emerged. Comparable dissociation constants K d were obtained for the unlabeled and labeled targets in direct or competitive binding assays. The enantiomeric tracer was prepared and its enantioselective recognition by the corresponding anti ‐ D ‐Tym aptamer was demonstrated. The access to both enantiomeric tracer molecules opens the door for the development of one‐pot determination of the enantiomeric excess when using different labels with well‐separated redox potentials for each enantiomer.