Tan_2017_Nat.Commun_8_1760

Reference

Title : Multicomponent mapping of boron chemotypes furnishes selective enzyme inhibitors - Tan_2017_Nat.Commun_8_1760
Author(s) : Tan J , Cognetta AB, 3rd , Diaz DB , Lum KM , Adachi S , Kundu S , Cravatt BF , Yudin AK
Ref : Nat Commun , 8 :1760 , 2017
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 alpha- and beta-aminocyano(MIDA)boronates from borylated carbonyl compounds. Activity-based protein profiling of the resulting beta-aminoboronic acids furnishes selective and cell-active inhibitors of the (ox)lipid-metabolizing enzyme alpha/beta-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.

PubMedSearch : Tan_2017_Nat.Commun_8_1760
PubMedID: 29170371
Gene_locus related to this paper: human-ABHD3 , mouse-abhd3

Related information

Inhibitor MIDA-ester-4j    FP-Biotin
Gene_locus MIDA-ester-4j    FP-Biotin    human-ABHD3    mouse-abhd3

Citations formats

Tan J, Cognetta AB, 3rd, Diaz DB, Lum KM, Adachi S, Kundu S, Cravatt BF, Yudin AK (2017)
Multicomponent mapping of boron chemotypes furnishes selective enzyme inhibitors
Nat Commun 8 :1760

Tan J, Cognetta AB, 3rd, Diaz DB, Lum KM, Adachi S, Kundu S, Cravatt BF, Yudin AK (2017)
Nat Commun 8 :1760