부산대학교 도서관

On the basis of the high affinity of Zn2+ to sulfur and imidazole, we targeted nucleotides such as GDP-ß-S, ADP-β-S, and AP3(β-S)A, as potential biocompatible Zn2+-chelators. The thiophosphate moiety enhanced the stability of the Zn2+-nucleotide complex by about 0.7 log units. ATP-aß-CH2-y-S formed the most stable Zn2+-complex studied here, log K 6.50, being ~0.8 and ~1.1 log units more stable than ATP-y-S-Zn2+ and ATP-Zn2+ complexes, and was the major species, 84%, under physiological pH. Guanine nucleotides Zn2+ 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. 1H- and 3IP NMR monitored Zn2+ titration showed that Zn2+ 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 Zn2+-complexes of the latter analogues by up to 0.7 log units. A terminal phosphorothioate contributed more to the stability of nucleotide-Zn2+ complexes than a bridging phosphorothioate. [ABSTRACT FROM AUTHOR]