A DNA G-quadruplex adopting a (3+1) hybrid structure was modified in two
adjacent syn positions of the antiparallel strand with anti-favoring
2'-deoxy-2'-fluoro-riboguanosine (F rG) analogues. The two
substitutions promoted a structural rearrangement to a topology with the
5'-terminal G residue located in the central tetrad and the two modified
residues linked by a V-shaped zero-nucleotide loop. Strikingly, whereas a sugar
pucker in the preferred north domain is found for both modified nucleotides, the
F rG analogue preceding the V-loop is forced to adopt the unfavored
syn conformation in the new quadruplex fold. Apparently, a preferred C3'-endo
sugar pucker within the V-loop architecture outweighs the propensity of the
F rG analogue to adopt an anti glycosidic conformation. Refolding
into a V-loop topology is likewise observed for a sequence modified at
corresponding positions with two riboguanosine substitutions. In contrast,
2'-F-arabinoguanosine analogues with their favored south-east sugar conformation
do not support formation of the V-loop topology. Examination of known
G-quadruplexes with a V-shaped loop highlights the critical role of the sugar
conformation for this distinct structural motif.
