Benzimidazole covalent probes and the gastric H(+)/K(+)-ATPase as a model system for protein labeling in a copper-free setting.
Mol Biosyst
; 12(6): 1772-80, 2016 05.
Article
em En
| MEDLINE
| ID: mdl-26952080
ABSTRACT
Affinity probes are useful tools for determining molecular targets and elucidating mechanism of action for novel, bioactive compounds. In the case of covalent inhibitors, activity based probes are particularly valuable for ensuring acceptable selectivity margins. However, there is a variety of bioorthogonal chemistry reactions available for modifying compounds of interest with clickable tags. Here, we describe a direct comparison of tetrazine ligation and strain promoted azide-alkyne cycloaddition using benzimidazole based probes to bind their known target, the gastric proton pump, ATP4A. This study validates the use of chemical probes for target identification and illustrates the superior efficiency of tetrazine ligation for copper-free click systems. In addition, we have identified several novel binding partners of benzimidazole probes Isoform 2 of deleted in malignant brain tumors 1 protein (DMBT1) and three uncharacterized proteins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzimidazóis
/
Sondas Moleculares
/
ATPase Trocadora de Hidrogênio-Potássio
/
Inibidores da Bomba de Prótons
Idioma:
En
Revista:
Mol Biosyst
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos