Engineering Tethered DNA Molecules by the Convertible Nucleoside Approach

Article abstract of DOI:10.1016/S0040-4020(01)81793-2

Non-natural functional groups, tethered to DNA, provide a chemical handle for the site-specific attachment of reporter and effector elements.Herein we report a general strategy for the synthesis of oligodeoxynucleotides bearing tethered functionality (functionally tethered oligonucleotides, FTOs).In this approach, the convertible nucleoside 4-O-(2,4,6-trimethylphenyl)-2'-deoxyuridine (TMP-dU) is introduced site-specifically into DNA during automated synthesis.Upon treatment with aqueous amines, the TMP-dU moiety undergoes nucleophilic substitution to yield an N⁴-alkyl-dC nucleoside - the DNA product is a dC-tethered FTO.Since the tether structure is solely determined by choice of amine used in the deprotection/conversion reaction, this convertible nucleoside approach permits a wide variety of FTOs to be synthesized from a single precursor.