title: DNA-Encoded Dynamic Combinatorial Chemical Libraries.
abstract: Dynamic combinatorial chemistry (DCC) explores the thermodynamic equilibrium of reversible reactions. Its application in the discovery of protein binders is largely limited by difficulties in the analysis of complex reaction mixtures. DNA-encoded chemical library (DECL) technology allows the selection of binders from a mixture of up to billions of different compounds; however, experimental results often show low a signal-to-noise ratio and poor correlation between enrichment factor and binding affinity. Herein we describe the design and application of DNA-encoded dynamic combinatorial chemical libraries (EDCCLs). Our experiments have shown that the EDCCL approach can be used not only to convert monovalent binders into high-affinity bivalent binders, but also to cause remarkably enhanced enrichment of potent bivalent binders by driving their in situ synthesis. We also demonstrate the application of EDCCLs in DNA-templated chemical reactions.
authors.affiliation: B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, Dresden 01307 (Germany).
authors.forename: Francesco V
authors.initials: FV
authors.lastname: Reddavide
authors.affiliation: B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, Dresden 01307 (Germany).
authors.forename: Weilin
authors.initials: W
authors.lastname: Lin
authors.affiliation: B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, Dresden 01307 (Germany).
authors.forename: Sarah
authors.initials: S
authors.lastname: Lehnert
authors.affiliation: B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, Dresden 01307 (Germany). yixin.zhang@bcube-dresden.de.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D001710:Biotin / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000378:metabolism; D020650:Combinatorial Chemistry Techniques; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D055808:Drug Discovery; D015723:Gene Library; D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D019809:Streptavidin / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries; C518163:iminobiotin; D001710:Biotin; D004247:DNA; D019809:Streptavidin
keywords: DNA-encoded chemical libraries; DNA-templated reactions; drug discovery; dynamic combinatorial chemistry; protein-ligand interactions