Hiroki Gazuma
Pharmacia, 2021, 57(8), 771
https://doi.org/10.14894/faruawpsj.57.8_771

Abstract

Screening using a DNA-encoded library (DEL) is a useful drug discovery method. DEL is a trillion-scale compound library that binds compounds and DNA and associates compound information with DNA sequences. The DEL compound is assayed against the immobilized target protein and then washed away to select the compound that interacts with the target protein. DNA is excised from these compounds and their sequences are read to identify the chemical structure. Since DNA can be amplified by PCR, it is a great merit that even a very small amount of compound can be evaluated.
On the other hand, in order to construct a large-scale DEL, it is necessary to select a reaction that proceeds in water in the presence of alcohols and amines contained in DNA, even under the condition of using a low concentration (1 mM) compound. Therefore, the substrates and reaction conditions that can be used are limited, and there is a problem that the diversity of DEL is difficult to increase, and the development of reaction conditions to solve this problem is required. Coupling reactions using metal catalysts are useful for DEL construction, but are limited to sp2 carbon coupling. Yu et al. Reported the C-H bond activation reaction of sp3 carbon, which is effective for the construction of various DELs, and will be introduced in this volume.
This paper introduces the research results based on the following documents.