title: An innovative method to study target protein-drug interactions by mass spectrometry.
abstract: We report the combination of chemical cross-linking and high-resolution mass spectrometry for analyzing conformational changes in target proteins that are induced by drug binding. With this approach conformational changes in the peroxisome proliferator-activated receptor alpha (PPARalpha) upon binding of low-molecular weight compounds were readily detected, proving that the strategy provides a basis to efficiently characterize target protein-drug interactions.
authors.affiliation: Department of Pharmaceutical Chemistry and Bioanalytics, Institute of Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, D-06120 Halle/Saale, Germany.
authors.forename: Mathias Q
authors.initials: MQ
authors.lastname: Müller
authors.forename: Leo J
authors.initials: LJ
authors.lastname: de Koning
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmidt
authors.forename: Christian
authors.initials: C
authors.lastname: Ihling
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Syha
authors.forename: Oliver
authors.initials: O
authors.lastname: Rau
authors.forename: Karl
authors.initials: K
authors.lastname: Mechtler
authors.forename: Manfred
authors.initials: M
authors.lastname: Schubert-Zsilavecz
authors.forename: Andrea
authors.initials: A
authors.lastname: Sinz
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D006868:Hydrolysis; D008024:Ligands; D013058:Mass Spectrometry; D008958:Models, Molecular; D010080:Oxazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D015203:Reproducibility of Results; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: C449302:GW 6471; D008024:Ligands; D010080:Oxazoles; D047493:PPAR alpha; D004364:Pharmaceutical Preparations; D014443:Tyrosine