Switching the type of V-loop in sugar-modified G-quadruplexes through altered fluorine interactions

Mixed 2'-F-riboguanosine and 2'-F-arabinoguanosine disubstitutions of a hybrid-type G-quadruplex are found to induce a refolding into two alternative structures with different types of V-loops upon positional exchange of the two G analogs. While conformational preferences of the incorporated G surrogates fail to fully account for the observed rearrangements, additional hydrogen bonds with a fluorine acceptor are suggested to be critical determinants of the two distinct V-loop conformers imposing different tetrad polarities.