ODN synthesis, deprotection, cleavage, purification and characterization: All ODNs were synthesized on an MerMade 6 synthesizer on the Dmoc support 2j (26 µmol/g loading, 20 mg, 0.52 µmol) using phosphoramidite chemistry. Deblocking: DCA (3%, DCM), 90 sec × 2. Coupling: Phosphoramidite (2a-d, 2f-i, and 2e for incorporating dC, dA, dG, T, 4acC, 6acA, 2acG, 4mcC, and the T at 5′-end of ODN, respectively; 0.1 M, ACN), 4,5-dicyanoimidazole (DCI, 0.25 M, ACN), 90 sec × 3. Capping: 2-Cyanoethyl N,N,N′,N′-tetraisopropylphosphoramidite (0.1 M, ACN), DCI (0.25 M, ACN), 60 sec × 3. Oxidation: I 2 (0.02 M, THF/pyridine/H 2 O, 70:20:10, v/v/v), 40 sec × 3. At the end of the synthesis, the 5'-trityl group was kept. The CPG (3, Figure ) was divided into 5 equal portions (~0.104 µmol ODN each). One portion was subject to deprotection and cleavage. Removing 2-cyanoethyl groups: The suspension of CPG (3, ~0.104 µmol ODN) in the solution of DBU in ACN (1:9, v/v, 1 mL) in a 1.5 mL centrifuge tube was gently shaken at rt for 5 min. The supernatant was removed. The process was repeated two more times. The CPG was washed with ACN (1 mL × 5). This converted 3 to 4. Oxidizing meDmoc and Dmoc: The suspension of 4 in the solution of NaIO 4 (0.4 M, 1 mL), which has a pH of 4, in a 1.5 mL centrifuge tube was gently shaken at rt for 1.5 h. The supernatant was removed. The process was repeated two times. The CPG was washed with water (1 mL × 5). This converted 4 to 5. Removing oxidized meDmoc groups: The suspension of 5 in the solution of K 2 CO 3 (0.05%, 1 mL), which has a pH of 8, in a 1.5 mL centrifuge tube was gently shaken at rt for 5 h. The supernatant was transferred into a clean 1.5 mL centrifuge tube. The CPG was washed with water (150 μL × 5). The combined supernatant and washes were concentrated to ∼50 μL. To the solution was added nBuOH (450 μL). After mixing by vortex, ODN was precipitated via centrifugation (14.5k rpm, ~14k × g, 15 min). The supernatant was removed leaving deprotected ODN (6) in the tube. RP HPLC purification: ODN (6) was dissolved in H 2 O (100 μL). A portion (35 μL) was purified with RP HPLC (see supporting information for HPLC conditions). The fractions of the Tr-on ODN were combined and concentrated to dryness. To the ODN was added AcOH (80%, 1 mL). The mixture was shaken gently at rt for 3 h. Volatiles were evaporated. The residue was dissolved in water (100 μL), and a portion (50 μL) was purified with RP HPLC. The purified Tr-off ODN was analyzed with RP HPLC. The ODNs were quantified using a reported method [21], and analyzed with MALDI MS. The dissolve-spin desalting method was used for preparing samples for the MS analysis when needed . The purity of the ODNs was further confirmed with capillary gel electrophoresis and PAGE.