Binding Ensemble Profiling with Photoaffinity Labeling (BEProFL) Approach: Mapping the Binding Poses of HDAC8 Inhibitors

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2009 Nov 6

PMID 19886628

Citations 14

Authors

Bai He

Subash Velaparthi

Gilles Pieffet

Chris Pennington

Aruna Mahesh

Denise L Holzle

Michael Brunsteiner

Richard van Breemen

Sylvie Y Blond

Pavel A Petukhov

Affiliations

Soon will be listed here.

Abstract

A binding ensemble profiling with (f)photoaffinity labeling (BEProFL) approach that utilizes photolabeling of HDAC8 with a probe containing a UV-activated aromatic azide, mapping of the covalent modifications by liquid chromatography-tandem mass spectrometry, and a computational method to characterize the multiple binding poses of the probe is described. By use of the BEProFL approach, two distinct binding poses of the HDAC8 probe were identified. The data also suggest that an "upside-down" pose with the surface binding group of the probe bound in an alternative pocket near the catalytic site may contribute to the binding.

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