Creation of Conformationally Rigid Bent and Linear Nucleic Acids by 3-Dimensional Fixation of Conformation of Mono- and Di-nucleotide Building Blocks

In this article, two kinds of cyclic systems to construct sterically locked pU and UpU derivatives were reviewed. One is the bridged structure between the 5-postion of the uracil moiety and the 5'-phosphate group. In this case, the use of a propylene alkyl chain as the bridged structure resulted in induction of the C3'-endo conformation in the ribose moiety which is observed in the typical A-type RNA duplex. Incorporation of this structural motif (pc3U) into the 3'-downstream U of UpU shows that its C3'-endo conformation was preserved but the sugar puckering of the 5'-upstream U was orientated to a C2'-endo form. The use of UBNA and pc3U as the 5'-upstream and 3'-downstream uridine components, respectively, resulted in formation of two P-chiral diastereoisomers, namely, linear- and benttype dimers of UBNApc3U. Oligonucleotides incorporating the linear-type dimer showed strong hybridization affinity for the complementary strand. Oligonucleotides incorporating the bent-type dimer exhibited no significant hybridization affinity for the complementary RNA strand. However, the bent structural motif showed significant thermal stability when incorporated into the U-turn region of the tRNA anticodon stem and loop. Another cyclic UpU system having a largemembered ring structure was introduced to create the conformationally locked Uturn structure. The bridged structures having amide and urethane linkages were used. Oligonucleotides having these cyclic structural UpU motifs showed significant rigidity but the conformation of the two uridine sugar moieties was not fixed in the C3'-endo form. Finally, a cyclic UpU derivative was designed as an ideal U-turn mimic. This dimer has 3'-deoxy-3'-aminouridine and 2'-deoxy-2'- fluorouridine derivatives as the 5'-upstream and 3'-downstrem components. The bridged structure was constructed between the 2'-hydroxyl group of the 5'- upstream U and the 5-position of the 3'-downstream U via a propyrene chain. The detailed studies of the cyclic UpU revealed that this compound has a U-turn bent structure having a rigid CD spectrum.