An important functional group, benzo[1,3]dioxole, of alkaloids induces the formation of the human telomeric DNA G-quadruplex

The Interaction of Telomeric DNA and C-myc22 G-Quadruplex with 11 Natural Alkaloids

“…Tep has a chiral carbon that connects rings B and C with H , this conformation can decrease the planarity and increase the steric hindrance. Fourth, previous study revealed that a larger number of benzo[1,3]dioxole groups of ligands increase the ability to interact with G4 (Yang et al, 2011). According to our results, it is not the number of the benzo [1,3]dioxole groups that affect the interaction with G4, but whether the group can help built a good planar structure ( Supplementary Fig.…”

“…We applied melting-CD to monitor the melting temperature (Tm) ( Table 2) of induced G4 formed by Hum6 and Hum24 at 262 nm to discuss the stabilities. The change in Tm (DT) (Table 2) in the folded and unfolded G4 structures upon interacting with the ligands provides evidence of thermal stabilization of the DNA structure (Yang et al, 2011). We found an obvious increase in Tm with the presence of S1 except Tep ( Supplementary Fig.…”

“…It seemed that the functional part of S2 was their parent structure. To small molecules with p-aromatic surfaces of fewer than 2 rings, neither the position of the positively charged centers nor the substitutions could adjust their ability to interact with G4 (Yang et al, 2011). From the structure of S2, we can see that they have no more than 2 consecutive rings, but linked by some loops; this may be the reason that the substituents do not affect the ability to interact with G4 so much.…”

“…CD Spectroscopy has been extensively applied to study secondary structures of DNA. Different DNA structures have distinct CD spectral features, which can be used to recognize different DNA motifs conveniently (Yang et al, 2010c(Yang et al, , 2011. We applied CD to investigate the G4-inducing ability of S1.…”

“…Since the first report on the interaction between small molecules and G4 DNA in 1997 (Wang et al, 2010), many leading compounds that target G4 have been found, including anthraquinones (Sun et al, 1997;Perry et al, 1998aPerry et al, , 1998b, cationic porphyrins (Anantha et al, 1998;Han et al, 2001), perylene (Rossetti et al, 2002), benzoindoloquinolines (Alberti et al, 2002, ethidium derivatives (Koeppel et al, 2001), acridine derivatives (Harrison et al, 1999), piperazines (Riou et al, 2001), pentacyclicacridinium salts (Gowan et al, 2001), fluoroquinophenoxazines (Duan et al, 2001), and others. Most of these compounds have the same features: (1) a p-delocalized system that is able to stack on the face of a guanine quartet, (2) a partial positive charge that is able to lay in the center of the quartet, increasing stabilization by substituting the cationic charge of the potassium or sodium that would normally occupy that site, and (3) positively charged substituents to interact with the grooves and loops of G4 and the negatively charged backbone phosphates (Reed et al, 2006;Yang et al, 2011). In accordance with these desirable features, there are 3 interaction modes of G4-ligands and G4: (1) external stacking: ligands stack on the terminal Gquarter through p-p accumulation; (2) intercalating: ligands insert into the space of two G-quarters; and (3) groove binding: ligands bind to the grooves or loops of the G4.…”