High-throughput sequencing allows the identification of binding molecules isolated from DNA-encoded chemical libraries

Luca Mannocci; Yixin Zhang; Jörg Scheuermann; Markus Leimbacher; Gianluca De Bellis; Ermanno Rizzi; Christoph Dumelin; Samu Melkko; Dario Neri
Proc. Natl. Acad. Sci. USA, 2008, 105(46), 17670-5
https://doi.org/10.1073/pnas.0805130105

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.

logo
logo