Design and synthesis of a possible mimic of a thrombin-binding DNA aptamer

A synthesis is presented of the cyclic trimeric d-oligonucleotide 3′-isopropylphosphate I, comprising one formacetal and two (3′ → 5′)-internucleosidic phosphodiester bonds. The ester linkages connect d-guanosine with the 3′ and 5′ ends of thymidine and 5-hydroxymethyl-2′-deoxyuridine-3′-isopropylphosphate (HMDUpiPr), respectively. The 5′-end of the thymidine unit is anchored via the formacetal bond to the allylic hydroxyl group of HMDUpiPr. The cyclic arrangement of the three d-nucleosides in I mimics, as based on molecular modeling, the key structural features of the conformationally constrained T7pG8pT9p-domain of the thrombin-binding DNA aptamer d(G1G2T3T4G5G6 T 7 G 8 T 9 G10G11T12T13G14G15). Biological evaluation showed that compound I did not exhibit anti-thrombin activity.