High-throughput screening for ADP-ribosyl hydrolase 3 inhibitors
Farmer, Rachel Elizabeth
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https://hdl.handle.net/2142/109637
Description
Title
High-throughput screening for ADP-ribosyl hydrolase 3 inhibitors
Author(s)
Farmer, Rachel Elizabeth
Issue Date
2020-12-08
Director of Research (if dissertation) or Advisor (if thesis)
Hergenrother, Paul J.
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
M.S.
Degree Level
Thesis
Keyword(s)
ARH3
PAR
Screen
Abstract
Poly(ADP-ribose) (PAR) signaling is an important component of DNA damage repair, DNA replication, and initiation of parthanatos, a method of controlled cell death. While PAR has been well studied for decades, much is still unknown about PAR’s initiation of parthanatos and the importance of mono(ADP-ribose) (MAR) in cellular regulation. The lack of knowledge in this field can be attributed in part to the lack of a cell-permeable tool compound to study the activity of ARH3, a key degrader of PAR and MAR. Toward filling this need, a high-throughput screen was conducted using a fluorogenic substrate to discover an inhibitor of ARH3. A total of 496 primary hits have been identified and will be further studied to validate their ability to inhibit ARH3.
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