Scheme 5. Synthesis of DNA-linked ponatinib fragments. (A) Acceptor conjugates. (B) Donor conjugates. Reagents and conditions: (a) (i) CuSO₄, THPTA, sodium ascorbate, phosphate buffer (100 mM NaH₂PO₄/Na₂HPO₄, pH 7.4), H₂O, DMSO, 30 °C, 3 h, Ar; (ii) TCEP, rt, 30 min, 28%; (b) (i) H₂O, DMSO, rt, 22 h; (ii) TCEP, rt, 30 min, 32%; (c) CuSO₄, THPTA, sodium ascorbate, phosphate buffer (100 mM NaH₂PO₄/Na₂HPO₄, pH 7.4), H₂O, DMSO, 60 °C, 6 h, Ar, 37%; (d) HATU, DIPEA, H₂O, DMF, rt, 4 h, 15%. DNA1 = 5′-TTGAACTCTGCTTAAATCCAG-3′. DNA2 = 5′-CCGCTGAAGGGCTT-3′.