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Related Experiment Videos

DMSO-related effects in protein characterization.

Agneta Tjernberg1, Natalia Markova, William J Griffiths

  • 1Department of Lead Discovery, Biovitrum AB, Stockholm, Sweden. agneta.tjernberg@biovitrum.com

Journal of Biomolecular Screening
|February 24, 2006
PubMed
Summary

Dimethyl sulfoxide (DMSO) can alter protein stability and binding properties in drug discovery assays. Early studies are crucial to understand these DMSO effects on proteins and ensure reliable results.

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Area of Science:

  • Biochemistry
  • Drug Discovery
  • Analytical Chemistry

Background:

  • Dimethyl sulfoxide (DMSO) is a common solvent for preparing compound stock solutions in drug discovery.
  • Typical assay concentrations range from 0.1% to 5% (v/v), making DMSO a frequent assay buffer additive.
  • Standardization does not prevent potential pitfalls from DMSO's effects on individual proteins.

Purpose of the Study:

  • To emphasize the importance of studying DMSO's effects on proteins early in drug discovery.
  • To investigate DMSO's impact on protein stability, aggregation, and drug binding.
  • To assess DMSO's influence on electrospray ionization mass spectrometry (ESI-MS) ionization.

Main Methods:

  • Studied two protein systems: human growth hormone receptor (hGHbp) and PFKFB1 phosphatase domain (BPase).

Related Experiment Videos

  • Assessed effects of low DMSO concentrations on protein stability and aggregation.
  • Evaluated changes in drug compound binding properties in the presence of DMSO.
  • Analyzed DMSO's influence on ESI-MS ionization processes.

    • Main Results:

    • Significant differences in protein behavior were observed with low DMSO concentrations.
    • DMSO addition led to destabilization of the studied proteins.
    • Apparent binding properties of one protein were altered by DMSO.
    • Low DMSO concentrations were found to influence ESI-MS ionization.

    Conclusions:

    • Even low concentrations of DMSO can significantly impact protein behavior, including stability and binding.
    • Detailed studies on DMSO's effects are essential in early drug discovery stages.
    • DMSO's influence extends to analytical techniques like ESI-MS, affecting ionization processes.