Synthesis and pairing properties of oligoribonucleotide analogues containing a metal-binding site attached to beta-D-allofuranosyl cytosine.
A method for the facile preparation of oligoribonucleotide analogues containing beta-d-allofuranosyl nucleosides with additional functional groups tethered to the 6'-O positions is presented. It is based on the synthesis of 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, respectively, each capable of complexing metal ions. By automated synthesis, these functionalized nucleoside analogues were efficiently incorporated into short oligoribonucleotides. Under physiological conditions (150 mM NaCl, 2 mM MgCl2, pH 7.4), incorporation of a single allofuranosyl 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.
Wu
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Organisch-Chemisches Laboratorium der Eidgenössischen Technischen Hochschule, Universitätstrasse 16,CH-8092 Zürich, Switzerland.
Pitsch
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D001665:Binding Sites; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D008670:Metals / Q000737:chemistry; D015394:Molecular Structure; D009843:Oligoribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*
D008670:Metals; D009843:Oligoribonucleotides; C115333:allofuranosyl cytosine; D003596:Cytosine