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Design of Boron-Based Peptidomimetics Leads to Potent Inhibitors of Human ClpP and ClpXP

preprint
submitted on 30.11.2018 and posted on 03.12.2018 by Joanne Tan, Julie Jungberg Grouleff, Yulia Jitkova, Diego Diaz, Elizabeth Griffith, Wenjie Shao, Anastasia Bogdanchikova, Gennady Poda, Aaron Schimmer, Richard Lee, Andrei Yudin

Boronic acids have attracted the attention of synthetic and medicinal chemists due to boron’s ability to modulate enzyme function. Recently, we demonstrated that boron-containing amphoteric building blocks facilitate the discovery of bioactive aminoboronic acids. Herein, we have augmented this capability with a de novo library design and virtural screening platform modified for covalent ligands. This technique has allowed us to rapidly design and identify a series of α-aminoboronic acids as the first inhibitors of human ClpXP, which is responsible for the degradation of misfolded proteins.

History

Email Address of Submitting Author

ayudin@chem.utoronto.ca

Institution

University of Toronto

Country

Canada

ORCID For Submitting Author

0000-0003-3170-9103

Declaration of Conflict of Interest

No conflict of interest.

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