Sweet Binders: Carbonic Anhydrase IX in Complex with Sucralose
Carrie L Lomelino1, Akilah B Murray1, Claudiu T Supuran2
1Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida 32610, United States.
ACS Medicinal Chemistry Letters
|July 24, 2018
Summary
Sucralose selectively binds to carbonic anhydrase IX (CA IX), a key target in hypoxic tumors. Structural analysis reveals active site properties for designing novel anticancer drugs and CA IX inhibitors.
Area of Science:
- Biochemistry
- Structural Biology
- Medicinal Chemistry
Background:
- Carbonic anhydrase IX (CA IX) regulates pH in hypoxic tumors.
- CA IX is a promising therapeutic target for various cancers.
- Sweeteners like sucrose, saccharin, and acesulfame potassium show selectivity for CA IX.
Purpose of the Study:
- To determine the X-ray crystal structure of a CA IX-mimic in complex with sucralose.
- To understand the structural basis for CA IX isoform-specific inhibition.
- To facilitate the design of new anticancer drugs targeting CA IX.
Main Methods:
- X-ray crystallography to determine the structure of CA IX-mimic bound to sucralose at ~1.5 Å resolution.
- Comparative structural analysis with other sweetener/carbohydrate studies.
- Analysis of active site properties influencing selective binding.
Main Results:
- The crystal structure of the CA IX-mimic-sucralose complex was determined.
- Structural comparison identified key active site features promoting selective sucralose binding to CA IX.
- Insights into CA IX isoform-specific inhibition mechanisms were gained.
Conclusions:
- Structural insights into sucralose binding enhance understanding of CA IX inhibition.
- This knowledge aids in designing more effective CA IX inhibitors.
- Facilitates the development of novel anticancer therapeutics targeting hypoxic tumors.
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