High-throughput sequencing allows the identification of binding molecules isolated from DNA-encoded chemical libraries.
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.
Mannocci
Luca
L
Institut für Pharmazeutische Wissenschaften Departement für Chemie und Angewandte Biowissenschaften, Eidgenössische Technische Hochschule, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Zhang
Yixin
Y
Scheuermann
Jörg
J
Leimbacher
Markus
M
De Bellis
Gianluca
G
Rizzi
Ermanno
E
Dumelin
Christoph
C
Melkko
Samu
S
Neri
Dario
D
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
D007074:Immunoglobulin G; D054852:Small Molecule Libraries; D004247:DNA; D019809:Streptavidin; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3