Loop flexibility in human telomeric quadruplex small-molecule complexes.
Bottom Line: Sugar conformation and backbone angles have also been examined and trends highlighted.One particular loop class has been found to be most prevalent.Implications for in particular, rational drug design, are discussed.
Affiliation: UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.Show MeSH
Related in: MedlinePlus
Mentions: The overwhelming majority of quadruplex-binding small molecules reported to date possess planar groupings and their mode of binding predominantly involves 3′ or 5′ end-stacking onto terminal G-quartets (Figure 1). Intercalative binding has not been observed experimentally for these ligands and is widely considered not to be consistent with biophysical data on quadruplex-small molecule complexes (11–13). A small number of quadruplex-binding ligands, mostly based on a polyamide motif, have been proposed to bind in quadruplex grooves rather than on G-quartet surfaces. There is no detailed experimental structural information on their interaction with human telomeric bimolecular or unimolecular quadruplexes and so groove-binding structures will not be considered any further here.
Affiliation: UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.