A Novel Branch-Type PEGylation of Aptamer Therapeutics

We have developed a novel protocol to prepare a branch-type PEGylation for a long acting formulation of aptamer therapeutics. A symmetric doubler phosphoramidite and the following amine modified phosphoramidite synthon were introduced to the final sequence of antithrombin aptamer, as a model for various aptamer therapeutics. The conventional linear PEGylation reagents were conjugated to the terminal amine groups of oligonucleotide to prepare the branchtype PEGylated anti-thrombin DNA aptamer. The PEGylated aptamer exhibited the improved bioactivity to retard the occlusive thrombus formation in vitro.