Characterization of complexes of nucleoside-5'-phosphorothioate analogues with zinc ions
| Autor: | Noa Stern, Yehudit Itzhakov, Alon Haim Sayer, Yael Nadel, Bilha Fischer |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
inorganic chemicals
Magnetic Resonance Spectroscopy Guanine Stereochemistry Inorganic chemistry Thiophosphate Inorganic Chemistry chemistry.chemical_compound Drug Stability Adenine nucleotide Coordination Complexes Imidazole Moiety Nucleotide Physical and Theoretical Chemistry Chelating Agents chemistry.chemical_classification Molecular Structure Nucleosides Hydrogen-Ion Concentration Thionucleotides Phosphate Adenosine Monophosphate Zinc chemistry biological sciences health occupations bacteria Nucleoside |
| Zdroj: | Inorganic chemistry. 52(19) |
| ISSN: | 1520-510X |
| Popis: | On the basis of the high affinity of Zn(2+) to sulfur and imidazole, we targeted nucleotides such as GDP-β-S, ADP-β-S, and AP3(β-S)A, as potential biocompatible Zn(2+)-chelators. The thiophosphate moiety enhanced the stability of the Zn(2+)-nucleotide complex by about 0.7 log units. ATP-α,β-CH2-γ-S formed the most stable Zn(2+)-complex studied here, log K 6.50, being ~0.8 and ~1.1 log units more stable than ATP-γ-S-Zn(2+) and ATP-Zn(2+) complexes, and was the major species, 84%, under physiological pH. Guanine nucleotides Zn(2+) complexes were more stable by 0.3-0.4 log units than the corresponding adenine nucleotide complexes. Likewise, AP3(β-S)A-zinc complex was ~0.5 log units more stable than AP3A complex. (1)H- and (31)P NMR monitored Zn(2+) titration showed that Zn(2+) coordinates with the purine nucleotide N7-nitrogen atom, the terminal phosphate, and the adjacent phosphate. In conclusion, replacement of a terminal phosphate by a thiophosphate group resulted in decrease of the acidity of the phosphate moiety by approximately one log unit, and increase of stability of Zn(2+)-complexes of the latter analogues by up to 0.7 log units. A terminal phosphorothioate contributed more to the stability of nucleotide-Zn(2+) complexes than a bridging phosphorothioate. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|