Cognetta_2015_Chem.Biol_22_928

Reference

Title : Selective N-Hydroxyhydantoin Carbamate Inhibitors of Mammalian Serine Hydrolases - Cognetta_2015_Chem.Biol_22_928
Author(s) : Cognetta AB, 3rd , Niphakis MJ , Lee HC , Martini ML , Hulce JJ , Cravatt BF
Ref : Chemical Biology , 22 :928 , 2015
Abstract :

Serine hydrolase inhibitors, which facilitate enzyme function assignment and are used to treat a range of human disorders, often act by an irreversible mechanism that involves covalent modification of the serine hydrolase catalytic nucleophile. The portion of mammalian serine hydrolases for which selective inhibitors have been developed, however, remains small. Here, we show that N-hydroxyhydantoin (NHH) carbamates are a versatile class of irreversible serine hydrolase inhibitors that can be modified on both the staying (carbamylating) and leaving (NHH) groups to optimize potency and selectivity. Synthesis of a small library of NHH carbamates and screening by competitive activity-based protein profiling furnished selective, in vivo-active inhibitors and tailored activity-based probes for multiple mammalian serine hydrolases, including palmitoyl protein thioesterase 1, mutations of which cause the human disease infantile neuronal ceroid lipofuscinosis.

PubMedSearch : Cognetta_2015_Chem.Biol_22_928
PubMedID: 26120000

Related information

Inhibitor MJN193    ABC47    ABC51    JJH221    ABC44
Substrate MJN193    ABC47    ABC51    JJH221    ABC44    NAPE

Citations formats

Cognetta AB, 3rd, Niphakis MJ, Lee HC, Martini ML, Hulce JJ, Cravatt BF (2015)
Selective N-Hydroxyhydantoin Carbamate Inhibitors of Mammalian Serine Hydrolases
Chemical Biology 22 :928

Cognetta AB, 3rd, Niphakis MJ, Lee HC, Martini ML, Hulce JJ, Cravatt BF (2015)
Chemical Biology 22 :928