Synthesis And Properties Of Purine Nucleoside And Nucleotide Derivatives

Nucleoside and nucleotide derivatives are important antivirus and antitumor drugs. More and more novel bioactivity nucleoside analogs come forth continuously because the structure of nucleoside is easy to modify, such as anticancer drug, antivirus drug, lowering blood pressure drug and so on. Synthesis, biochemical activity assay and drug choosing of novel nucleoside and nucleotide derivatives are becoming the research focus recently. Studies on this field were described in this paper. The content of this paper was consisted of two parts as follows:1. According to reference, nucleoside derivativeε-G was synthesized successfully and was characterized by ¹H NMR,EA,FT-IR. The formation mechanism of new imidazole was also studied. Ultraviolet and fluorescence spectra ofε-G at various pH were studied. The results indicated that the interaction betweenε-G and BSA were. The results indicated thatε-G had different form at different pH.ε-G had strength fluorescence at pH 7.40. The wavelength ofε-G excitation and emission was 262 nm and 438 nm, respectively. It's out of the absorbance range of protein and nucleotide. In this condition, the results studied interaction betweenε-G and BSA by fluorescence spectra showed that fluorescence quenching existed between them. Fluorescence quenching type of BSA initiated byε-G was static quenching, while the concentration ofε-G was low 8.0×10^-5 mol·L^-1 . The binding constant and the number of binding sites betweenε-G and BSA were determined, which were 1.78×10³L·mol^-1 and 1, respectively. While the concentration ofε-G was up 8.0×10^-5mol·L^-1', fluorescence quenching type of BSA was combined quenching (both static and dynamic). The fluorescence ofε-G at various organic solvents was studied. The results showed that fluorescence ofε-G enhanced along with the strengthening in solvents polarity.2. 2-Amnio-6-chloro-purine nucleoside triphosphate and 2-amino-ATP were synthesized firstly by the chemical method and were characterized by ¹H NMR, ³¹P NMR, ¹³C NMR, EA and FT-IR. Ultraviolet and fluorescence properties of them at various pH were studied. Their pK_a were determined by the relation of UV and pH. 2-Amino-6-chloro-PNTP had one pK_a and its value was 1.44. 2-Amino-ATP had two pK_a and their values were 0.68 and 4.83, respectively. The results were close to the values calculated from ACD/Labs software. The wavelength of 2-amino-6-chloro-PNTP and 2-amino-ATP excitation was 285 nm and 280 nm and the corresponding emission was 366 nm and 346 nm at pH 6.50, respectively. In addition, hydrolysis of 2-amino-6-chloro-PNTP and 2-amino-ATP by potato apyrase was studied. The competing mechanism to potato apyrase between ATP analogs and ATP was also studied. Fluorescence yield of 2-amino-ATP was 0.03 with quinine as standard. The UV of 2-amino-ATP changed with various organic solvents. Surrounding polar and poton properties had great influence on 2-amino-ATP.