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DNA-encoded chemistry: enabling the deeper sampling of chemical space
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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.Abstract:
DNA-encoded chemistry enables rapid and inexpensive syntheses and screening of vast chemical libraries, and is generating substantial interest and investment in the pharmaceutical industry. Here, Goodnow and colleagues provide an overview of the steps involved in the generation of DNA-encoded libraries, highlighting key applications and future directions for this technology. 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.read more
Citations
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Ultra-large library docking for discovering new chemotypes
Jiankun Lyu,Sheng Wang,Trent E. Balius,Isha Singh,Anat Levit,Yurii S. Moroz,Matthew J. O’Meara,Tao Che,Enkhjargal Algaa,Kateryna A. Tolmachova,Andrey A. Tolmachev,Brian K. Shoichet,Bryan L. Roth,John J. Irwin +13 more
TL;DR: Using a make-on-demand library that contains hundreds-of-millions of molecules, structure-based docking was used to identify compounds that, after synthesis and testing, are shown to interact with AmpC β-lactamase and the D4 dopamine receptor with high affinity.
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Expanding the medicinal chemistry synthetic toolbox
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Chemistries for DNA Nanotechnology.
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Impact of a five-dimensional framework on R&D productivity at AstraZeneca
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TL;DR: The evolution of the approach to target validation, hit and lead optimization, pharmacokinetic/pharmacodynamic modelling and drug safety testing, which have helped improve the quality of candidate drug nomination, as well as the development of the right culture.
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DNA-Encoded Chemical Libraries: A Selection System Based on Endowing Organic Compounds with Amplifiable Information.
Dario Neri,Richard A. Lerner +1 more
TL;DR: This review provides a historical account of important milestones in the development of DNA-encoded chemical libraries, a survey of relevant ongoing research activities, and a glimpse into the future.
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