Synthesis of oligonucleotide having a bent structure by incorporation of an interresidually cyclized uridylyl (3'-5')uridine unit.

ABSTRACT

The chemical synthesis and conformational properties of interresidually cyclized uridylyl(3'-5')uridine derivatives were studied in order to introduce a stable turn structure into oligonucleotides. These cyclized molecules were analogs of uridylyl(3'-5')5-[methylamino(methyl)]-uridine which is the component of the U turn structure of tRNAarg E. coli. The conformational properties of these cyclic dinucleoside monophosphates were studied using NMR and CD spectroscopy with the aid of molecular mechanics and molecular dynamics simulations. These experiments indicated that the turn conformation could be stabilized by introducing a cyclic structure as expected. On the basis of these results, the chemical synthesis of phosphoramidite units of these cyclic dinucleoside monophosphate derivatives were studied to construct oligonucleotides having a stable bent structure.