Understanding self-assembly at molecular level enables controlled design of DNA G-wires of different properties.

A possible engineering of materials with diverse bio- and nano-applications relies on robust self-assembly of oligonucleotides. Bottom-up approach utilizing guanine-rich DNA oligonucleotides can lead to formation of G-wires, nanostructures consisting of continuous stacks of G-quartets. However, G-wire structure and self-assembly process remain poorly understood, although they are crucial for optimizing properties needed for specific applications. Herein, we use nuclear magnetic resonance to get insights at molecular level on how chosen short, guanine-rich oligonucleotides self-assemble into G-wires, whereas complementary methods are used for their characterization. Additionally, unravelling mechanistic details enable us to guide G-wire self-assembly in a controlled manner. MD simulations provide insight why loop residues with considerably different properties, i.e., hydrogen-bond affinity, stacking interactions, electronic effects and hydrophobicity extensively increase or decrease G-wire length. Our results provide fundamental understanding of G-wire self-assembly process useful for future design of nanomaterials with specific properties.

GC ends control topology of DNA G-quadruplexes and their cation-dependent assembly.

GCn and GCnCG, where n = (G2AG4AG2), fold into well-defined, dimeric G-quadruplexes with unprecedented folding topologies in the presence of Na+ ions as revealed by nuclear magnetic resonance spectroscopy. Both G-quadruplexes exhibit unique combination of structural elements among which are two G-quartets, A(GGGG)A hexad and GCGC-quartet. Detailed structural characterization uncovered the crucial role of 5'-GC ends in formation of GCn and GCnCG G-quadruplexes. Folding in the presence of 15NH4+ and K+ ions leads to 3'-3' stacking of terminal G-quartets of GCn G-quadruplexes, while 3'-GC overhangs in GCnCG prevent dimerization. Results of the present study expand repertoire of possible G-quadruplex structures. This knowledge will be useful in DNA sequence design for nanotechnological applications that may require specific folding topology and multimerization properties.