Methyl-Phosphate H-Bonds

In a feat of molecular manipulation, the methyl and phosphate groups in a selenium-derivatized DNA molecule have for the first time been brought close enough together to form hydrogen bonds, reports Zhen Huang and coworkers of Georgia State University (Org. Lett., DOI: 10.1021/ol9004867). Huang's group synthesized thymidine with a selenium atom inserted between the C-5 carbon of the base and its methyl group. The methyl group is usually 4–5 Å away from the closest oxygen of the backbone phosphate, but the selenium linker extends the methyl toward the phosphate. It also provides enough rotational flexibility so that the methyl can turn away from the phosphate into the major groove of the DNA to avoid steric hindrance if there is no hydrogen bonding taking place. The X-ray crystal structure of DNA made with the selenium-modified thymidine reveals that the distance between the methyl and phosphate groups is only 2.93 Å, which is within the typical H-bond distance. Huang suspects that such interactions may play a role in processes that involve unwinding DNA. "This interaction definitely helps reduce the energy barrier for duplex unwinding in replication and transcription, which may also explain why DNA has a regular methyl group but RNA does not," Huang says.