An aptamer combined with a fluorophore could work as the fluorescent core of nucleic acid mimics of
fluorescent proteins to locate and image functional biomolecules in cells. The locating precision comes
from the selective recognition between the compound and the aptamer. Recently, a fluorescent probe
with a triazine ring was reported to selectively recognize the c-MYC Pu22 G-quadruplex (G4) in vitro
and ex vivo, but the weak binding limits its application as a fluorescent response core. Through
structure-based screening and optimization, we identified a compound (DPQ) with a novel pyrazolo[4,3-
c]quinoline core exhibiting selective light-up fluorescence and stronger binding affinity with c-MYC
promoter G4s (Kd = 2.35 mM for c-MYC Pu22 G4). The conformation comparison between the crystal
structure of free DPQ and its conformation with the c-MYC Pu22 G4 indicated that the fluorescence
enhancement came from the induced fitting of DPQ to the G4 pocket. The complex of DPQ and
c-MYC Pu22 G4 provides a potential fluorescent response core to construct a new DNA mimic of
fluorescent proteins to track or locate functional nucleic acid units. |
