title: High-throughput sequencing allows the identification of binding molecules isolated from DNA-encoded chemical libraries.
abstract: DNA encoding facilitates the construction and screening of large chemical libraries. Here, we describe general strategies for the stepwise coupling of coding DNA fragments to nascent organic molecules throughout individual reaction steps as well as the first implementation of high-throughput sequencing for the identification and relative quantification of the library members. The methodology was exemplified in the construction of a DNA-encoded chemical library containing 4,000 compounds and in the discovery of binders to streptavidin, matrix metalloproteinase 3, and polyclonal human IgG.
authors.affiliation: Institut für Pharmazeutische Wissenschaften Departement für Chemie und Angewandte Biowissenschaften, Eidgenössische Technische Hochschule, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Mannocci
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jörg
authors.initials: J
authors.lastname: Scheuermann
authors.forename: Markus
authors.initials: M
authors.lastname: Leimbacher
authors.forename: Gianluca
authors.initials: G
authors.lastname: De Bellis
authors.forename: Ermanno
authors.initials: E
authors.lastname: Rizzi
authors.forename: Christoph
authors.initials: C
authors.lastname: Dumelin
authors.forename: Samu
authors.initials: S
authors.lastname: Melkko
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
mesh_terms: D004247:DNA / Q000032:analysis*; D005454:Fluorescence Polarization; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007700:Kinetics; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods*; D054852:Small Molecule Libraries / Q000737:chemistry*; D019809:Streptavidin / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D054852:Small Molecule Libraries; D004247:DNA; D019809:Streptavidin; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3