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1H-NMR effects in chloroquine-biopolymer binding interactions
Physiological Chemistry and Physics
|January 1, 1979
Summary
Chloroquine (CQ) concentrates in lysosomes, but binding to lysosomal proteins is weak. Evidence supports a proton-pump trapping model, not simple protein affinity, for CQ uptake.
Area of Science:
- Biochemistry
- Pharmacology
- Cell Biology
Background:
- Chloroquine (CQ) is an antimalarial and anti-inflammatory drug known for lysosomal accumulation.
- Understanding the mechanism of CQ uptake into lysosomes is crucial for its therapeutic applications.
Purpose of the Study:
- To investigate the binding interactions of chloroquine (CQ) with lysosomal components.
- To elucidate the mechanism behind CQ's concentration within lysosomes.
Main Methods:
- 1H-NMR spectroscopy was employed to study CQ binding.
- CQ binding was assessed with purified proteins (albumin, butyrylcholinesterase, DNA) and isolated rodent liver lysosome fractions (matrix and membrane).
- Triton WR-1339 and sucrose were used to assess potential contaminant effects.
Main Results:
- CQ demonstrated interactions with albumin, butyrylcholinesterase, and high molecular weight DNA, indicated by line-width changes.
- Lysosomal matrix and membrane fractions showed relatively weak interactions with CQ, with membranes being more retentive.
- Contaminants Triton WR-1339 and sucrose had minimal effects beyond viscosity.
- Estimated binding constants were too low to explain CQ lysosomal accumulation via protein affinity.
Conclusions:
- The observed weak binding interactions do not fully explain chloroquine's lysosomal accumulation.
- The findings support the proton-pump trapping model for CQ uptake, as proposed by de Duve et al.
- Further research into lysosomal transport mechanisms is warranted.