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

Article abstract of DOI:10.1016/S0960-894X(97)00351-X

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(G¹G²T³T⁴G⁵G⁶T⁷G⁸T⁹G¹⁰G¹¹T¹²T¹³G¹⁴G¹⁵). Biological evaluation showed that compound I did not exhibit anti-thrombin activity.