Toward RNase inhibitors: thermodynamics of 2'-CMP/RNase-A binding in multi-ion buffer
| Autor: | Robert B. Raffa, Robert J Schulingkamp, Shawn D. Spencer |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Isothermal microcalorimetry Binding Sites biology RNase P Stereochemistry Cytidine Ribonuclease Pancreatic Buffers Biochemistry chemistry.chemical_compound Enzyme chemistry Enzyme inhibitor Metals biology.protein Cytidine Monophosphate Animals Thermodynamics Pancreatic ribonuclease Cattle Ribonuclease Binding site Enzyme Inhibitors |
| Zdroj: | Biochemical pharmacology. 63(11) |
| ISSN: | 0006-2952 |
| Popis: | Certain ribonucleases (RNases), such as eosinophil-derived neurotoxin, are associated with pathological conditions (e.g. asthma and inflammatory bowel disease) and can even be overtly cyto(neuro)toxic. It has been proposed that small-molecule inhibitors should have therapeutic utility. We used isothermal titration microcalorimetry to characterize reversible inhibitor cytidine 2'-monophosphate (2'-CMP) binding to RNase-A in a multi-ion buffer at 37 degrees as a representative system. The estimated parameters were: K(d)=13.9 microM; DeltaG degrees =-6.90 kcal/mol; DeltaH degrees =-15.7 kcal/mol; and DeltaS degrees =-0.028 kcal/mol-K ('enthalpy-driven' interaction). These data should assist drug design of small-molecule inhibitors of homologous RNase catalytic domains. |
| Databáze: | OpenAIRE |
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