Dendrimers and Brancher Phosphoramidites

Dendrimers are discrete, highly branched, monodispersed polymers that possess patterns reminiscent of the branching of trees. Plain and mixed oligonucleotide dendrimers can be synthesized using novel doubling and trebling phosphoramidite synthons.1,2 Dendrimers offer the following advantages. Incorporation of label using g-32P-ATP and polynucleotide kinase increases in proportion to the number of 5'-ends. Fluorescent signal also increases in proportion to the number of 5'-ends, if spacers are incorporated between the labels and the ends of the branches. When using a dendrimeric oligonucleotide as a PCR primer, the strand bearing the dendrimer is resistant to degradation by T7 Gene 6 exonuclease making it easy to convert the double-stranded product of the PCR to a multiply labelled, single-stranded probe. Enhanced stability of DNA dendrimers makes them useful as building blocks for the 'bottom up' approach to nano-assembly. These features also suggest applications in DNA chip technology when higher temperatures are required, for example, to melt secondary structure in the target.

A branching monomer is  required to construct comb-like oligonucleotide probes.  The developers of the comb system from Chiron Corporation evaluated³ several protecting groups for the branch point and chose levulinyl (LEV), which is specifically removed using a reagent containing hydrazine hydrate, acetic acid and pyridine.