Synthesis and Properties of Oligothymidylates Incorporating an Artificial Bend Motif

The uridylyl‐(3′→5′)‐thymidine dinucleotide block 14 (cUpdU), having a cyclic structure between the 2′‐hydroxy of the upstream uridine and the 5‐substituent of the downstream thymidine, was synthesized (Schemes 1 and 2). This cyclic structure is a stable mimic of the intraresidual H‐bonding found in the anticodon loop of an E. coli minor tRNA^Arg. The spectroscopic and molecular‐mechanics analyses of the cyclized dinucleotides predicted two major conformers, i.e., the turn and bent forms. The latter was expected to bend DNA oligomers when incorporated into them. This expectation was ascertained by incorporating the bent dimer motif into tetra‐, deca‐, or hexadecathymidylates by the conventional phosphoramidite method (see 18 – 20 in Scheme 4). The bending of oligonucleotides 18 – 20 was demonstrated by ³¹P‐NMR and CD spectra and gel‐electrophoretic studies. The duplex formation of these modified oligonucleotides with oligodeoxyadenylates was also studied. The decreased thermal stability of the duplexes when compared with unmodified ones indicates distorted structures of the modified duplexes. The 3D computer model of the duplexes showed a bend of ca. 30° with a `bulge‐out' at the position of an adenosine residue facing the cyclized dimer. The artificially bent DNAs might become a new tool for the study of the effect of DNA bending induced in DNA/DNA‐binding protein interactions.