DNA Encoding the Diversity of Chemical Space
Speaker: Dr. Hongtao Xu 许红涛
Invited by Ge Jiang
Time: 3:00 pm, Jul. 17 (Friday), 2020
Venue: Room C801, Y Building, ShanghaiTech
Abstract
DNA-encoded library (DEL) links the power of genetics and chemical synthesis. It comprises millions or even billions of DNA-tagged small molecules, which can be effectively synthesized via combinatorial chemistry and screened against various protein targets of interest in a single pooled assay. Screening of DELs has emerged as a validated technology to interrogate the infinite chemical space. Advanced DELs have delivered several promising hits for chemical biology probes design or drug development. DEL hits have been proved to active for the challenging targets on the allosteric binding sites, protein−protein interaction surfaces, and oligonucleotide binding sites.
Despite these progresses, the great potential of DEL technology in drug discovery has not yet fully realized. One of the most fundamental challenge is the synthesis of high-quality libraries with more structural diversity, which in turn depends on the development of new and robust DNA-compatible reactions that allow more flexibility in DEL’s design and synthesis. In order to circumvents such limitation we have developed a series of methodology that can be used for on-DNA labelling of natural products (nDEL) or on-DNA synthesis of diversity oriented DELs.
