Synthesis and pairing properties of oligoribonucleotide analogs containing a metal-binding site attached to b-D-allofuranosyl cytosine

A method for the facile prepn. of oligoribonucleotide analogs contg. b-D-allo-furanosyl nucleosides with addnl. functional groups tethered to the 6'-O positions is presented. It is based on the synthesis in two protected nucleosides carrying a 6'-O-bromopentyl and a 6'-O-methylaminopentyl substituent. By a simple two-step procedure, these key intermediates were transformed into two phosphoramidites carrying a 1-aza-18-crown-6 and a triethyleneglycol group, resp., each capable of complexing metal ions. By automated synthesis, these functionalized nucleoside analogs were efficiently incorporated into short oligoribonucleotides. Under physiol. conditions (150 mM NaCl, 2 mM MgCl2, pH 7.4), incorporation of a single allo-furanosyl cytosine substituted with a triethyleneglycol moiety led to a significant enthalpic stabilization of an A-type RNA duplex. This observation is in agreement with a metal ion-mediated stabilizing interaction between the two pairing strands. [on SciFinder (R)]