Target-guided selection of DNA-encoded chemical libraries for macrocycle ligand discovery
Grant Data
Project Title
Target-guided selection of DNA-encoded chemical libraries for macrocycle ligand discovery
Principal Investigator
Professor Li, Xiaoyu
(Principal Investigator (PI))
Duration
36
Start Date
2020-09-01
Completion Date
2024-08-19
Amount
666512
Conference Title
Target-guided selection of DNA-encoded chemical libraries for macrocycle ligand discovery
Keywords
DNA-encoded library, drug discovery, high-throughput screening, macrocycles, target-guided synthesis
Discipline
Chemical SciencesDrug Discovery and Delivery
Panel
Physical Sciences (P)
HKU Project Code
17303220
Grant Type
General Research Fund (GRF)
Funding Year
2020
Status
Completed
Objectives
1 To develop a DNA-encoded library method capable of synthesizing linear precursor libraries with high chemical diversity; 2 To develop a DNA-encoded library method capable of selecting macrocycle ligands against a broad range of biological targets from a linear precursor library, which uses strategies of target-guided cyclization and cyclative cleavage 3 To identify potent and specific macrocyclic ligands with novel chemotypes for representative protein targets, including PPIs, protein complexes, and membrane PPI targets, followed by validating the biological functions of the identified ligands. 4 To explore the capability of the method in identifying macrocycle ligands against PPI targets on live cells. 5 To summarize the results and identify future research opportunities for more in-depth studies, with the aim to develop novel therapeutics for protein targets that are intractable to traditional ligand screening methods.