Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds

Scheme 4

Synthesis of MGB polyamide-oligonucleotide conjugates. Reagents and conditions: i Oligonucleotide assembly on CPG support by the phosphoramidite method, 3% Cl₃CCO₂H, CH₂Cl₂; 0.05 M phosphoramidite 17, 0.25 M 1H-tetrazole, CH₃CN, or CH₂Cl₂; Ac₂O, 2,6-lutidine, 1-methylimidazole, THF; and 0.02 M I₂, H₂O/pyridine/THF. (ii) 3% Cl₃CCO₂H, CH₂Cl₂; 0.1 M FmocNH-(CH₂)_nNH-MGB polyamide 12, 13, 14, 15, 29, 30, 31, 35, 36, or 37, 1 : 5 Et₃N/1,4-dioxane, 60°C, 24 h; 0.5 M DBU, pyridine, rt, 12 h. Conc. NH₄OH, rt., 2 h–55°C, and 6 h.