Phosphoramidites of base-modified 2′-deoxyinosine isosteres and solid-phase synthesis of d(GCI*CGC) oligomers containing an ambiguous base

摘要

Novel phosphoramidites (1,2) of appropriately protected 2′-deoxyinosine isosteres (I*) such as allopurinol 2′-deoxy-ribofuranoside (4a) and 7-deaza-2′-deoxyinosine (4b) have been synthesized. They were employed together with the phosphorami-dite of 2′-deoxyinosine in solid-phase synthesis of d(GCI*CGC) hexamers (12a-d). From thermodynamic data of these alternating hexamers it was shown that allopurinol 2′-deoxyribofuranoside destabilizes such duplexes less strongly than 2′-deoxyinosine. Additionally, the phosphoramidite of 7-deaza-2′-deoxyinosine (2) exhibits an extraordinary stability of the N-glycosylic bond. Since the new phosphoramidites are structurally related to 2′-deoxyinosine, they can be used in the construction of hybridization probes containing an ambiguous base.