De Novo Design of Boron-Based Peptidomimetics as Potent Inhibitors of Human ClpP in the Presence of Human ClpX.
J Med Chem
; 62(13): 6377-6390, 2019 07 11.
Article
in En
| MEDLINE
| ID: mdl-31187989
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Boronic Acids
/
Endopeptidase Clp
/
Peptidomimetics
Limits:
Humans
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2019
Type:
Article
Affiliation country:
Canada