|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|
|Date Published||2019 Jul 11|
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.
|Alternate Journal||J. Med. Chem.|