“One Ring to Bind Them All”—Part II: Identification of Promising G-Quadruplex Ligands by Screening of Cyclophane-Type Macrocycles

Figure 1

(a) Structure of BOQ₁. (b) Side-view of the lowest-energy conformation of BOQ₁ during the molecular dynamic simulation. (c) FRET-melting results obtained with telomestatin, TMPyP4, and BOQ₁ (1 𝜇M), for experiments carried out with 0.2𝜇M F21T in lithium cacodylate buffer (10 mM, pH 7.2) with NaCl (100 mM), in the absence (black bars) or in the presence of 3 (dark green bars) or 10 𝜇M (light green bars) of double-stranded competitor (ds26). (It is worth noting that the FRET-melting values obtained herein for BOQ₁ differ from that of the initial publication (see [9]). This discrepancy originates in the different experimental conditions used, given that FRET-melting is performed herein as an HTS unlike the initial report (single-cell experiment); the disparities between the two methods are extensively detailed in [15] (among which can be cited the final volume (25 versus 600 𝜇L), the buffer conditions (10 mM lithium cacodylate + 100 mM NaCl versus 10 mM sodium cacodylate, 100 mM LiCl), etc.).)