|
Fig. 1 Crystal structure of an NBTI representative (AMK12; compound 1) developed in our laboratories in ternary complex with the Staphylococcus aureus DNA gyrase and oligonucleotide (PDB ID: 6Z1A) (Reck et al., 2012). For clarity purpose, two ciprofloxacin molecules were inserted artificially, indicating the difference in binding sites between fluoroquinolones and NBTIs. The protein is shown as a light blue ribbon, the oligonucleotide as a beige ribbon, while the NBTI (hot pink) and fluoroquinolones (yellow) are portrayed in stick representation and color coded by element. The symmetrical bifurcated halogen bonds are represented as orange dashes. On the right: the main structural features of the NBTI molecule (compound 1); the “left-hand side” (LHS) and the “right-hand side” (RHS) connected by the linker. Our design strategy includes a simple phenyl RHS, substituted in such a manner to allow symmetrical bifurcated halogen-bonding with the backbone carbonyl oxygens of both Ala68 residues.