Sheehan David, Lunstad Benjamin, Yamada Christina M, Stell Brian G, Caruthers Marvin H, Dellinger Douglas J
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
Nucleic Acids Res. 2003 Jul 15;31(14):4109-18. doi: 10.1093/nar/gkg439.
Phosphorus-modified phosphonoacetate and thiophosphonoacetate oligodeoxyribonucleotides were chemically synthesized and their biochemical properties evaluated. Under physiological pH, these DNA analogs possess negative charge and form stable, complementary A-like DNA:RNA heteroduplexes when analyzed via circular dichroism spectroscopy. Phosphonoacetate and thiophosphonoacetate oligomers were found to stimulate RNase H activity and to be completely resistant to degradation by snake venom phosphodiesterase, DNase I and HeLa cell nuclear extract. Further research has demonstrated that neutral, esterified forms of these analogs can be taken up by cells. Phosphonoacetate and thiophosphonoacetate oligomers therefore represent a new class of oligodeoxyribonucleotide analogs having phosphorus- carbon bonds with considerable potential for use in biological research.
磷修饰的膦酰乙酸酯和硫代膦酰乙酸酯寡脱氧核糖核苷酸经化学合成,并对其生化性质进行了评估。在生理pH值下,这些DNA类似物带有负电荷,通过圆二色光谱分析时,它们会形成稳定的、互补的A类DNA:RNA异源双链体。发现膦酰乙酸酯和硫代膦酰乙酸酯寡聚物能刺激RNase H活性,并且对蛇毒磷酸二酯酶、DNase I和HeLa细胞核提取物的降解具有完全抗性。进一步的研究表明,这些类似物的中性酯化形式可被细胞摄取。因此,膦酰乙酸酯和硫代膦酰乙酸酯寡聚物代表了一类新型的寡脱氧核糖核苷酸类似物,它们具有磷-碳键,在生物学研究中具有相当大的应用潜力。