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.
Design of Boron-Based Peptidomimetics Leads to Potent Inhibitors of Human ClpP and ClpXP
03 December 2018, Version 1
This content is a preprint and has not undergone peer review at the time of posting.
Design of boron-peptidomimetics leads to potent inhibitors of human ClpP and ClpXP