title: DNA-encoded chemistry: enabling the deeper sampling of chemical space.
abstract: DNA-encoded chemical library technologies are increasingly being adopted in drug discovery for hit and lead generation. DNA-encoded chemistry enables the exploration of chemical spaces four to five orders of magnitude more deeply than is achievable by traditional high-throughput screening methods. Operation of this technology requires developing a range of capabilities including aqueous synthetic chemistry, building block acquisition, oligonucleotide conjugation, large-scale molecular biological transformations, selection methodologies, PCR, sequencing, sequence data analysis and the analysis of large chemistry spaces. This Review provides an overview of the development and applications of DNA-encoded chemistry, highlighting the challenges and future directions for the use of this technology.
authors.affiliation: Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Waltham, Massachusetts 02451, USA.|Pharmaron, Inc., Boston, Massachusetts 02451, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Goodnow
authors.affiliation: Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel 4033, Switzerland.
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Dumelin
authors.affiliation: X-Chem, Waltham, Massachusetts 02453, USA.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Keefe
mesh_terms: D000818:Animals; D002621:Chemistry / Q000639:trends*; D004247:DNA / Q000235:genetics*; D055808:Drug Discovery / Q000639:trends; D015698:Genomic Library; D057166:High-Throughput Screening Assays; D006801:Humans; D054852:Small Molecule Libraries
chemical_list: D054852:Small Molecule Libraries; D004247:DNA