Carbonic anhydrase inhibitors: The very weak inhibitors dithiothreitol, β-mercaptoethanol, tris(carboxyethyl)phosphine and threitol interfere with the binding of sulfonamides to isozymes II and IX
| Autor: | Claudiu T. Supuran, Mikaela Lindfors, Seppo Parkkila, Markku S. Kulomaa, Henri R. Nordlund, Andrea Scozzafava, Alessio Innocenti, Mika Hilvo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Tris
Phosphines Stereochemistry Clinical Biochemistry Pharmaceutical Science Carbonic Anhydrase II Biochemistry Dithiothreitol chemistry.chemical_compound Sugar Alcohols Antigens Neoplasm Carbonic anhydrase Drug Discovery medicine Humans Carbonic Anhydrase IX Carbonic Anhydrase Inhibitors Threitol Molecular Biology Carbonic Anhydrases Mercaptoethanol chemistry.chemical_classification Molecular Structure biology Organic Chemistry Enzyme assay Acetazolamide Isoenzymes Enzyme chemistry Spectrophotometry Enzyme inhibitor biology.protein Molecular Medicine medicine.drug |
| Zdroj: | Innocenti, A, Hilvo, M, Scozzafava, A, Lindfors, M, Nordlund, H R, Kulomaa, M S, Parkkila, S & Supuran, C T 2008, ' Carbonic anhydrase inhibitors: The very weak inhibitors dithiothreitol, β-mercaptoethanol, tris(carboxyethyl)phosphine and threitol interfere with the binding of sulfonamides to isozymes II and IX ', Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 6, pp. 1898-1903 . https://doi.org/10.1016/j.bmcl.2008.02.008 |
| ISSN: | 1464-3405 0960-894X |
| DOI: | 10.1016/j.bmcl.2008.02.008 |
| Popis: | The inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) with dithiothreitol, 2-mercaptoethanol, tris(carboxyethyl)phosphine (reducing agent frequently added to enzyme assay buffers) and threitol has been investigated. The agents were very weak inhibitors of isozymes CA II and CA IX, but unexpectedly, strongly influenced the binding of the low nanomolar sulfonamide inhibitor acetazolamide (5-acetamido-1,3,4-thiadiazole-2-sulfonamide). Acetazolamide affinity for all investigated CAs diminished orders of magnitude with increasing concentrations of these agents in the assay system. DTT and similar derivatives should not be added to the assay buffers used in monitoring CA activity/inhibition, as they lead to under-estimation of the binding constants, by a mechanism probably involving the formation of ternary complexes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect