Telithromycin

Antibiotics were added to E. coli ribosomes at molar ratios (antibiotic–ribosome) ranging from 600 to 2600. The antibiotic protons relaxed slower (enhanced T_2obs) with a relative increase in antibiotic concentration (Fig. 2b). Fig. 3a shows titration plots of the observed selective T_2obs of the 6-OMe, the 3 -Me and the S-Me protons of telithromycin, roxithromycin and clindamycin, respectively. In 0.8 µM E. coli ribosome solution, antibiotic concentration dependence was evident (Figs. 2b, 3a, S1 and S2). The linearity of the plots illustrates the binding of the antibiotics to the bacterial ribosomes according to eqn. (1). The binding constant KD can thus be obtained from the y-intercept of the linear plot; for telithromycin, roxithromycin and clindamycin binding to the E. coli ribosomes, K_D = 1.2 × 10^-3, 1.3 × 10^-3 and 1.3 × 10^-2, respectively (Table 1). The value of KD was closely related to the antibacterial activity. Telithromycin (1) displayed a significantly better overall anti-biotic activity than did clindamycin (3), and at the same time, the K_D(1)/K_D(3) ratio (Fig. 4a) was in the range of 0.1–0.2 for their weak E. coli ribosomal interaction.