Title | De Novo Design of Boron-Based Peptidomimetics as Potent Inhibitors of Human ClpP in the Presence of Human ClpX. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Tan, J, Grouleff, JJ, Jitkova, Y, Diaz, DB, Griffith, EC, Shao, W, Bogdanchikova, AF, Poda, G, Schimmer, AD, Lee, RE, Yudin, AK |
Journal | J Med Chem |
Volume | 62 |
Issue | 13 |
Pagination | 6377-6390 |
Date Published | 2019 Jul 11 |
ISSN | 1520-4804 |
Abstract | 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 a virtual 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. |
DOI | 10.1021/acs.jmedchem.9b00878 |
Alternate Journal | J. Med. Chem. |
PubMed ID | 31187989 |