The construction of linear oligonucleotides on solid support is based on the sequential assembly of nucleoside phosphoramidites progressing from a 3' to 5' direction. The specific stepwise addition of the building block monomers provides a selective method for growing organized oligonucleotide structures of specific length and composition. The static environment of the solid support can act as template for the molecular assembly of discrete higher ordered oligonucleotide structures resembling those found within the cell  (i.e. branched RNA). We have established a novel approach for the creation of molecular entities based on novel branchpoint synthons. This solid phase methodology has been developed to construct symmetric and asymmetric branched and hyperbranched oligonucleotides based on RNA and RNA-DNA chimeras (msDNA). Their structures provide for chemical insight on the mechanism for synthetic chain assembly and stability of phosphate triesters on solid support. Moreover, these molecules have potentially desirable enzymatic properties and serve as probes for understanding key biological processes governing RNA splicing (e.g. debranching of lariat RNA).

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