About this Research Topic
DNA-encoded chemical library (DEL) has gained widespread acceptance in both major pharmaceutical companies and academic research within a short timeframe of the last decade. For example, a series of drug candidates developed by several major pharmas using DEL technology are already under clinical trials. Its popularity in drug discovery communities stems from a few key attributes of this particular brand of combinatorial chemistry, including direct coupling of chemical synthesis and bioactivity assay, direct readout of hits' structures based on DNA tags, high fidelity and sensitivity engendered by PCR reaction and dramatic cost reduction in storage space and material requirement as compared to conventional chemical libraries. In addition, recent activities in this field of research have shown great potentials of DEL technology beyond a binding assay, for example, as a powerful tool to explore fundamental biology, discover novel catalysts, and develop sequence-defined polymers.
Notwithstanding, severe limitations still exist in DEL synthesis and detection, hence great opportunities lie ahead, for example, stringent DNA-compatible reaction conditions, rather limited chemical space in today's libraries generated by dozens of available chemical reactions and, last but not least, protein-based assays in most cases.
Although several drug candidates developed have been advanced into clinical trials, the output from DEL screenings seems to less than optimal, given its widespread adoption by pharmaceutical industry today. One reason is that the compound libraries belong to relatively limited chemical space. This problem, in turn, can be traced to a small set of chemical reactions that can proceed well at present with good substrate scope and in good yields under stringent reaction conditions compatible with short-strand DNA tags. We anticipate several approaches to address the synthetic problems, such as adoption of existing complexity-generating reactions to water-based, DNA-compatible settings and development of new reactions and new reaction sequences and development of novel scaffolds in DEL libraries.
Today most of DEL screenings rely on purified proteins and are limited to protein-based binding assays. Screenings against other types of more complex biological targets, for example, DNA/RNAs, membrane proteins, protein complexes, live cells, tissue cultures, etc., still remain largely underexplored. Only in recent years, extracellular and intracellular whole cell-based assays have emerged, and more efforts are dedicating to realizing functional DEL selections. A few model systems have been reported on these fronts, but certainly more systematic and comprehensive studies will emerge in near future.
We invite submissions of Original Research, Review, Minireview and Perspective articles, in themes including, but not limited to:
• Reaction discovery related to DEL with new types of stereoselectivity and regioselectivity
• New reaction sequences that can give rise to new types of druglike scaffolds
• Novel bioassays that are developed for DEL screening
• Fundamental study on principles of DEL, such as data analysis and theoretical modelling
• Application of DEL technology in identification and optimization of lead compounds
• Application of DEL in other legacy or emerging techniques
• New DEL methods for non-biological applications such as catalyst discovery and functional materials.
Notwithstanding, severe limitations still exist in DEL synthesis and detection, hence great opportunities lie ahead, for example, stringent DNA-compatible reaction conditions, rather limited chemical space in today's libraries generated by dozens of available chemical reactions and, last but not least, protein-based assays in most cases.
Although several drug candidates developed have been advanced into clinical trials, the output from DEL screenings seems to less than optimal, given its widespread adoption by pharmaceutical industry today. One reason is that the compound libraries belong to relatively limited chemical space. This problem, in turn, can be traced to a small set of chemical reactions that can proceed well at present with good substrate scope and in good yields under stringent reaction conditions compatible with short-strand DNA tags. We anticipate several approaches to address the synthetic problems, such as adoption of existing complexity-generating reactions to water-based, DNA-compatible settings and development of new reactions and new reaction sequences and development of novel scaffolds in DEL libraries.
Today most of DEL screenings rely on purified proteins and are limited to protein-based binding assays. Screenings against other types of more complex biological targets, for example, DNA/RNAs, membrane proteins, protein complexes, live cells, tissue cultures, etc., still remain largely underexplored. Only in recent years, extracellular and intracellular whole cell-based assays have emerged, and more efforts are dedicating to realizing functional DEL selections. A few model systems have been reported on these fronts, but certainly more systematic and comprehensive studies will emerge in near future.
We invite submissions of Original Research, Review, Minireview and Perspective articles, in themes including, but not limited to:
• Reaction discovery related to DEL with new types of stereoselectivity and regioselectivity
• New reaction sequences that can give rise to new types of druglike scaffolds
• Novel bioassays that are developed for DEL screening
• Fundamental study on principles of DEL, such as data analysis and theoretical modelling
• Application of DEL technology in identification and optimization of lead compounds
• Application of DEL in other legacy or emerging techniques
• New DEL methods for non-biological applications such as catalyst discovery and functional materials.
Keywords: DNA-encoded library, encoded library technology, chemical library, drug discovery, high-throughout screening, ligand optimization
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