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DNA-Encoded Dynamic Combinatorial Chemical Libraries

Reddavide, Francesco V. ; Lin, Weilin ; Lehnert, Sarah ; Zhang, Yixin

Angewandte Chemie (International ed.), 2015-06, Vol.54 (27), p.7924-7928 [Periódico revisado por pares]

Weinheim: WILEY-VCH Verlag

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Título:
DNA-Encoded Dynamic Combinatorial Chemical Libraries
Autor: Reddavide, Francesco V. ; Lin, Weilin ; Lehnert, Sarah ; Zhang, Yixin
Assuntos: Binders ; Biotin - analogs & derivatives ; Biotin - isolation & purification ; Biotin - metabolism ; Combinatorial analysis ; Combinatorial chemistry ; Combinatorial Chemistry Techniques ; Deoxyribonucleic acid ; DNA ; DNA - chemistry ; DNA - metabolism ; DNA-encoded chemical libraries ; DNA-templated reactions ; Drug Discovery ; dynamic combinatorial chemistry ; Dynamics ; Enrichment ; Gene Library ; Libraries ; Ligands ; Protein Binding ; protein-ligand interactions ; Proteins ; Proteins - metabolism ; Small Molecule Libraries - chemistry ; Small Molecule Libraries - isolation & purification ; Small Molecule Libraries - metabolism ; Streptavidin - metabolism ; Thermodynamic equilibrium ; Thermodynamics
É parte de: Angewandte Chemie (International ed.), 2015-06, Vol.54 (27), p.7924-7928
Notas: Bundesministerium für Bildung und Forschung
ark:/67375/WNG-X5K5NWM7-B
ArticleID:ANIE201501775
Bundesministerium für Bildung und Forschung (BMBF; Grant Nos. 03Z2EN12 and 03Z2E511). We thank Peggy Berg and Ulrike Hofmann for technical support. We thank Andreas Hartmann for help with the Matlab enrichment simulation. We thank Elisa Mele for help with the design of the microfluidic setup. We thank Michael Thompson for critical reading of the manuscript.
BMBF - No. 03Z2EN12; No. 03Z2E511
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ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: 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. Selection goes dynamic: Dynamic combinatorial chemistry explores the thermodynamic equilibrium of reversible reactions. DNA‐encoded chemical libraries enable the selection of binders from compound mixtures. Now the advantages of DNA‐encoded dynamic combinatorial chemical libraries for the selection of protein binders from a myriad of compounds (see picture) and for DNA‐templated reactions are demonstrated.
Editor: Weinheim: WILEY-VCH Verlag
Idioma: Inglês

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DNA-Encoded Dynamic Combinatorial Chemical Libraries

Reddavide, Francesco V. ; Lin, Weilin ; Lehnert, Sarah ; Zhang, Yixin

Weinheim: WILEY-VCH Verlag

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