DESIGN AND SYNTHESIS OF A POSSIBLE MIMIC OF A THROMBIN-BINDING DNA APTAMER

A synthesis is presented of the cyclic trimeric d-oligonucleotide 3'-i sopropylphosphate I, comprising one formacetal and two (3' --> 5')-int ernucleosidic phosphodiester bonds, The ester linkages connect d-guano sine with the 3' and 5' ends of thymidine and ydroxymethyl-2'-deoxyuri dine-3'-isopropylphosphate (HMDUpiPr), respectively. The 5'-end of the thymidine unit is anchored via the formacetal bond to the allylic hyd roxyl group of HMDUpiPr. The cyclic arrangement of the three d-nucleos ides in I mimics, as based on molecular modeling, the key structural f eatures of the conformationally constrained T(7)pG(8)pT(9) p-domain of the thrombin-binding DNA aptamer 5)G(6)T(7)G(8)T(9)G(10)G(11)T(12)T(1 3)G(14)G(15)). Biological evaluation showed that compound I did not ex hibit anti-thrombin activity. (C) 1997 Elsevier Science Ltd.