Benzimidazole covalent probes and the gastric H(+)/K(+)-ATPase as a model system for protein labeling in a copper-free setting.

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.

journal_name

Mol Biosyst

journal_title

Molecular bioSystems

authors

Paresi CJ,Liu Q,Li YM

doi

10.1039/c6mb00024j

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

1772-80

issue

6

eissn

1742-206X

issn

1742-2051

journal_volume

12

pub_type

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