DNA-encoded libraries technology

DNA-encoded library technology has been utilized for more than 10 years. This technology enables billions of compounds to be screened within a highly miniaturized format, feicilitated by high-capacity DNA sequencing, and provides opportunities in identifying allosteric modulators. 

Table 10.1 Applications of DNA-encoded library technology on biological targets of therapeutic interests.

However, one key issue has prevented Nature s approach being applied to small molecules the information coded in DNA or RNA base sequences cannot be directly translated into small molecule structures with Nature s machinery. New technologies and platforms need to be designed and implemented. The DNA-encoded library has emerged as one of the most intriguing approaches towards this goal. 

Therefore, expanding DNA-compatible chemical reactions is one of the most critical tasks for further development of this technology for DNA-encoded library to generate hit molecules with drug-like or even lead-like structures. Liu and co-workers have attempted DNA-templated reaction in organic solvents assisted by detergents" and achieved some success, which may be a viable approach to address this issue. 

Naturally, not all the goals above can be feasibly achieved with the current state of the art, but we believe technological advancement and ingenious human input, as they have already done, will eventually accomplish these tasks and make DNA-encoded libraries indispensable tools in drug discovery. 

As sampling of chemical space will be even more sparse with increasing size of the molecules, it may be required to revert to other technologies like fragment-based screen, natural products, DNA-encoded libraries, or dynamic combinatorial chemistry to generate starting points for lead identification. 

As alternative to the use of compound collections in HTS, novel technologies such as DNA-encoded libraries or dynamic combinatorial chemistry have been developed. It will be exciting to see if hits generated with these new tools can be transformed into drugs on the market. 

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