posted on 2021-12-20, 13:03authored byGitali Devi, Fernaldo Richtia Winnerdy, Jason Cheng Yu Ang, Kah Wai Lim, Anh Tuân Phan
A four-stranded scaffold of nucleic
acids termed G-quadruplex (G4)
has found growing applications in nano- and biotechnology. Propeller
loops are a hallmark of the most stable intramolecular parallel-stranded
G4s. To date, propeller loops have been observed to span only a maximum
of three G-tetrad layers. Going beyond that would allow creation of
more stable scaffolds useful for building robust nanodevices. Here
we investigate the formation of propeller loops spanning more than
three layers. We show that native nucleotide sequences are incompatible
toward this goal, and we report on synthetic non-nucleotide linkers
that form a propeller loop across four layers. With the established
linkers, we constructed a four-layered intramolecular parallel-stranded
G4, which exhibited ultrahigh thermal stability. Control on loop design
would augment the toolbox toward engineering of G4-based nanoscaffolds
for diverse applications.