Solid-phase synthesis of dipeptide-conjugated nucleosides and their interaction with RNA

Dipeptide-conjugated nucleosides were efficiently synthesized from the intermediates of 3'-amino-3'-deoxy-nucleosides by using the solid-phase synthetic strategy with HOBt/HBTU (1-hydroxy-1H-benzotriazole/2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluoroborate) as the coupling reagents (Schemes 1-3). CD Spectra and thermal melting studies showed that the synthesized hydrophobic dipeptide-thymidine and -uridine derivatives 8a-8d. 13a-d, and 18 had a mild affinity with the polyA (.) polyU duplex and could induce the change of RNA conformation. The results also implied that the interaction of conjugates with RNA might be related to the sugar pucker conformation of the nucleoside.