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Ca2+ binding and translocating properties of diflunisal
G S Neigh1, V S Ananthanarayanan
1Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
Biochemistry and Molecular Biology International
|May 1, 1996
Summary
The anti-inflammatory drug diflunisal binds calcium (Ca2+) and magnesium (Mg2+) ions, undergoing conformational changes. Diflunisal facilitates Ca2+ transport across lipid bilayers, suggesting potential ionophore properties.
Area of Science:
- Biochemistry
- Pharmacology
- Physical Chemistry
Background:
- Diflunisal is an anti-inflammatory drug.
- Calcium (Ca2+) and magnesium (Mg2+) ions play crucial roles in biological systems.
- Understanding drug-ion interactions is vital for pharmacology.
Purpose of the Study:
- To characterize the binding of Ca2+ and Mg2+ to diflunisal.
- To investigate the drug-mediated transport of Ca2+ across a lipid bilayer.
- To explore the potential ionophoretic properties of diflunisal.
Main Methods:
- Fluorescence spectroscopy
- Difference absorption spectroscopy
- Unilamellar vesicles (1,2-dimyristoyl-sn-glycero-3-phosphocholine)
- Kinetic analysis
Main Results:
- Diflunisal binds Ca2+ and Mg2+ with high affinity (low microM Kd).
- Binding induces significant conformational changes in diflunisal.
- Diflunisal forms 1:2 cation:drug complexes with Ca2+ and 1:1 with Mg2+.
- Ca2+ is transported across lipid bilayers via a 1:2 Ca2+:diflunisal sandwich complex.
Conclusions:
- Diflunisal exhibits cation-binding and transport capabilities.
- The drug's interaction with cations in a lipid-mimetic solvent is similar to biological conditions.
- These findings suggest potential ionophore activity of diflunisal, relevant to its biological effects.