Spotlights on Recent JACS Publications.

发表于：Journal of the American Chemical Society · 年份：2020 · DOI：10.1021/jacs.0c01221 · 研究领域：Medicine

G-Quadruplexes are four-stranded helical structures that form in sections of nucleic acids with high guanine content. Because they are instrumental in the transcription and replication of oncogenes, they are promising targets for new cancer therapies. Researchers have found that these motifs dynamically shift conformation, with important biological implications. But they still do not understand exactly how this happens or how fast. Harald Schwalbe and co-workers investigate these questions in two G-quadruplex structures from the promoter regions of the cMYC oncogene and the human telomerase-reverse-transcriptase (hTERT) gene (DOI: 10.1021/jacs.9b10367). They prevented conformational changes in the G-quadruplexes by using protective groups to block hydrogen bonding and then released the block and traced the kinetics of refolding with time-resolved NMR. They compared these results with thermal hysteresis kinetics experiments. The team finds that shifts in conformation in these structures take place slowly, over hours. In the case of hTERT, the kinetics are consistent with unfolding of one form before refolding into a new one. Further exploration of these “long-lived folding intermediates” could help expand our understanding of how G-quadruplexes function. Deirdre Lockwood Ph.D.