Synthesis and characterization of the dinucleoside monophosphates containing 2'-fluoro-2'-deoxyadenosine.

Abstract

Three dinucleoside monophosphates containing 2'-fluor-2'-deoxyadenosine (dAfl), dAfl-dAfl, dAfl-A, and A-dAfl, were synthesized chemically. Characterization of these dimers has been performed by UV absorption, CD, and 1H NMR spectroscopies. The results showed that all three dimers have a stacked conformation with a geometry similar to that of A-A but with greater extent of base-base over-lapping than A-A. This interpretation is verified by the data of chemical shifts and coupling constants of 1H NMR study on these dimers (D. M. Cheng, L. S. Kan, P. O. P. Ts'o. S. Uesugi, Y. Takatsuka, and M. Ikehara unpublished data). All three dimers form 2U.1A complexes with poly(uridylic acid). The Tm of dAfl-dAfl.2poly(U) is higher than that of dAfl-A.2poly(U), which in turn is higher than that of A-dAfl.2poly(U). The NMR results clearly indicate that the conformation of the furanose of dAfl moiety in these dimers is more favored toward 3'-endo than 2'-endo puckering in comparison with the adenosine. The effects of 3' substituents on oligo- and polynucleotide conformation are also discussed.