Synthesis of labeled oligonucleotides through a new chemically cleavable linker

A synthesis of labeled oligonucleotides incorporating a new chemically cleavable linker (III) via a two-step method is described. The labeled oligomers obtained after cleavage and deprotection reactions [treatment with anhydrous tert-butylamine and dry methanol, 1:1 (v/v) for 12 h at room temperature, and lyophilization followed by subsequent reaction with aq NH₄OH and methylamine (40%), 1:1 (v/v) for 5 min at 65 °C] were analyzed by RP-HPLC. A distinctive feature of this protocol is that free oligomers can be recovered from their labeled analogs under mild conditions (0.2 M NaOH containing 0.5 M NaCl over 30 min at room temperature) and are comparable to the corresponding standard oligonucleotides (HPLC).