Multicomponent mapping of boron chemotypes furnishes selective enzyme inhibitors.
Nat Commun
; 8(1): 1760, 2017 11 24.
Article
em En
| MEDLINE
| ID: mdl-29170371
ABSTRACT
Heteroatom-rich organoboron compounds have attracted attention as modulators of enzyme function. Driven by the unmet need to develop chemoselective access to boron chemotypes, we report herein the synthesis of α- and ß-aminocyano(MIDA)boronates from borylated carbonyl compounds. Activity-based protein profiling of the resulting ß-aminoboronic acids furnishes selective and cell-active inhibitors of the (ox)lipid-metabolizing enzyme α/ß-hydrolase domain 3 (ABHD3). The most potent compound displays nanomolar in vitro and in situ IC50 values and fully inhibits ABHD3 activity in human cells with no detectable cross-reactivity against other serine hydrolases. These findings demonstrate that synthetic methods that enhance the heteroatom diversity of boron-containing molecules within a limited set of scaffolds accelerate the discovery of chemical probes of human enzymes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfolipases
/
Compostos de Boro
/
Inibidores Enzimáticos
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article