Discovery of covalent modifiers via the complexity to diversity strategy

Targeted covalent drugs have recently become integral parts of drug discovery. Given the advantages of high-throughput screening in drug discovery, many electrophilic fragment collections have been developed as a promising alternative to discover and validate novel targets. However, most covalent screening libraries consist of flat, low molecular weight compounds that are lacking in complexity and are incapable of addressing more complex targets, such as protein-protein interactions. To fill this gap, a library of 19 complex and diverse compounds containing electrophilic moieties has been synthesized and screened for anticancer activity in cell culture. The results from these studies suggest the potential for electrophilic natural product-like compounds to be used in the investigation of biological targets implicated in cancer.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2021

Author dc:creator

• Sawyer, Adam Michael

Contributors dc:contributor

• Hergenrother, Paul J

• Covalent modifiers
• targeted covalent inhibitors
• complexity to diversity
• complex molecule synthesis

Statement dc:rights

• Copyright 2021 Adam Sawyer

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/110875

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/110875