2.B.41. The Synthetic Unimolecular G-Quadruplex Sodium Transporter (UGQ-NaT) Family Kaucher et al. 2006 described the covalent post-modification of a hydrogen-bonded assembly with the subsequent formation of a potent transmembrane Na+ transporter. Olefin metathesis was used to cross-link all 16 guanosine subunits in a lipophilic G-quadruplex. The resulting unimolecular G-quadruplex folds in the environment of a phospholipid membrane and functions as a Na+ transporter as judged by fluorescence and 23Na+ NMR transport assays.
DNA G-quadruplexes are four-stranded globular nucleic acid secondary structures formed in specific G-rich sequences with biological significance, such as human telomeres and oncogene promoters. Chen and Yang 2012 focused on the unimolecular DNA G-quadruplexes, which readily form in solution under physiological conditions and are the most biologically relevant. Available structural data show a great conformational diversity of unimolecular G-quadruplexes that are amenable to small-molecule drug targeting. The relationships between sequence, structure, and stability of unimolecular DNA G-quadruplexes, as well as the recent progress on interactions with small-molecule compounds and insights into rational design of G-quadruplex-interactive molecules has been reviewed (Chen and Yang 2012).