New insights into the effect of molecular crowding environment induced by dimethyl sulfoxide on the conformation and stability of G-quadruplex

Abstract

Various structures of G-quadruplex in biosystems play an important role in different diseases and are often regulated by a variety of molecular crowding environments induced by internal and even external factors (e.g., a solvent). Dimethyl sulfoxide (DMSO), a universal solvent, has been widely used in biological studies and for drug therapy, but little is known regarding its effect on G-quadruplex structure and stability. Here, we report the influence of molecular crowding environment induced by DMSO on the conformation and stability of G-quadruplex structure. We show that the G-quadruplex-forming sequences such as human telomeric sequence, which may have diverse conformations in different environments, tend to convert their topologies to parallel structures under the molecular crowding stimulated by DMSO. Moreover, DMSO can increase the stability of the parallel and antiparallel topologies, especially the parallel G-quadruplex sequence c-kit, but not the hybrid topologies. Further analysis of c-kit using the CD and NMR technique, combined with the unique structural characteristics of c-kit, reveals that the crowding, dehydration and interaction of DMSO are conductive to the formation and stability of the parallel G-quadruplex. The present study suggests that, DMSO, a common solvent used in DNA experiments, may have a nonnegligible influence on the structure and stability of G-quadruplex.