Inhibition of phosphatase activity by positively-charged cyclodextrins
M Ghosh1, T C Sanders, R Zhang
1Department of Chemistry, Brown University, Providence, Rhode Island 02912, USA.
Organic Letters
|June 3, 2000
Summary
Aminocyclodextrins inhibit enzymes that break down phosphate esters by binding to them. This study reveals structural details of these complexes and their dissociation rates.
Area of Science:
- Biochemistry
- Chemical Biology
- Enzymology
Background:
- Aminocyclodextrins are known to bind phosphate esters, including biologically relevant molecules like phosphotyrosine.
- Phosphate ester hydrolysis is a crucial biochemical reaction catalyzed by various enzymes.
Purpose of the Study:
- To investigate the inhibitory effects of aminocyclodextrins on phosphate ester hydrolysis catalyzed by specific enzymes.
- To elucidate the structural basis of these inhibitory interactions using spectroscopic methods.
- To determine the dissociation kinetics of the formed complexes.
Main Methods:
- Enzyme inhibition assays using lambda-protein phosphatase and acid phosphatase.
- Rotating-frame Overhauser Effect SpectroscopY (ROESY) experiments for structural elucidation.
- Analysis of ROESY data to approximate dissociation rates of noncovalent complexes.
Main Results:
- Aminocyclodextrins effectively inhibit the hydrolysis of phosphate esters catalyzed by lambda-protein phosphatase and acid phosphatase.
- ROESY studies provided detailed structural information on the complexes formed between aminocyclodextrins and aryl phosphates.
- The dissociation rates of these noncovalent complexes were approximated using ROESY data.
Conclusions:
- Aminocyclodextrins serve as inhibitors of key enzymes involved in phosphate ester metabolism.
- The binding interactions are structurally characterized, offering insights into inhibitor design.
- Understanding complex stability and dissociation is crucial for developing effective enzyme modulators.
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