Influence of Dimehylsulfoxide on Protein-Ligand Binding Affinities

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Author(s) Cubrilovic, Dragana, Zenobi, Renato
Publication Type Journal Items, Publication Status: Published
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Title Influence of Dimehylsulfoxide on Protein-Ligand Binding Affinities
Author(s) Cubrilovic, Dragana
Zenobi, Renato
Journal or Series Title Analytical Chemistry
Volume Number 85
Issue Number 5
Start Page 2724
End Page 2730
ISSN 0003-2700
Publisher American Chemical Society
Publication Place Washington, D.C.
Publication Date 2013-03
Abstract Because of its favorable physicochemical properties, DMSO is the standard solvent for sample storage and handling of compounds in drug discovery. To date, little attention was given to how DMSO influences protein-ligand binding strengths. In this study we investigated the effects of DMSO on different noncovalent protein-ligand complexes, in particular in terms of the binding affinities, which we determined using nanoESI-MS. For the investigation, three different protein-ligand complexes were chosen: trypsin-Pefabloc, lysozyme-tri-N-acetylchitotriose (NAG(3)), and carbonic anhydrase-chlorothiazide. The DMSO content in the nanoESI buffer was increased systematically from 0.5 to 8%. For all three model systems, it was shown that the binding affinity decreases upon addition of DMSO. Even 0.5-1% DMSO alters the K-D values, in particular for the tight binding system carbonic anhydrase-chlorothiazide. The determined dissociation constant (K-D) is up to 10 times higher than for a DMSO-free sample in the case of carbonic anhydrase-chlorothiazide binding. For the trypsin-Pefabloc and lysozyme-NAG(3) complexes, the dissociation constants are 7 and 3 times larger, respectively, in the presence of DMSO. This work emphasizes the importance of effects of DMSO as a co-solvent for quantification of protein-ligand binding strengths in the early stages of drug discovery.
DOI 10.1021/ac303197p
Additional Notes Received 2 November 2012, Accepted 24 January 2013
Document Type Article
Publication Status Published
Language English
Assigned Organisational Unit(s) 03430
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NEBIS System Number 000005465
Source Database ID WOS-000317031600027
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  author = "Cubrilovic, Dragana and Zenobi, Renato",
  title = "{I}nfluence of {D}imehylsulfoxide on {P}rotein-{L}igand {B}inding {A}ffinities",
  journal = "Analytical Chemistry",
  year = 2013,
  volume = "85",
  number = "5",
  pages = "2724--2730",
  month = mar,

E-Citations record created: Mon, 13 May 2013, 07:11:32 CET