Table 1.

MIC₉₀ and thermodynamic data of biotinylated nucleosides.

Compound		MIC90, μMb	KD, nMa	ΔG, kcal/mola	ΔH, kcal/mola	-TΔS, kcal/mol	ΔTm, °C	PDB
14, Bio-AMS		0.78	0.865 ± 0.040	−12.4 ± 0.5	−18.9 ± 0.1	6.6 ± 0.1	14.5 ± 1.0	3rux
28		>100	0.753 ± 0.002	−12.4 ± 0.0	−20.2 ± 0.2	7.8 ± 0.2	12.2 ± 1.0	n.d.c
34		3.12	2.14 ± 0.08	−11.8 ± 0.2	−22.1 ± 0.2	10.3 ± 0.2	12.5 ± 0.5	n.d.c
36		1.56	0.540 ± 0.007	−12.6 ± 0.2	−23.5 ± 0.4	10.7 ± 0.4	14.5 ± 1.0	4xtv
46		3.12	0.933 ± 0.045	−12.3 ± 0.6	−23.2 ± 0.2	10.9 ± 0.3	13.0 ± 0.5	4xyw
47		1.25	0.627 ± 0.016	−12.6 ± 1.0	−19.1 ± 0.1	6.5 ± 0.2	19.2 ± 0.6	n.d.c
57		>100	0.027 ± 0.003	−14.4 ± 0.2	–29.3 ± 0.1	14.9 ± 0.1	17.0 ± 1.0	4xtx
63		1.25	0.614 ± 0.018	−12.6 ± 0.3	−24.3 ± 0.5	11.8 ± 0.5	15.2 ± 0.8	4xty
69		50.0	0.153 ± 0.000	−13.4 ± 0.0	−28.4 ± 0.6	14.7 ± 0.5	17.7 ± 0.8	4xtz
73		50.0	0.769 ± 0.006	−12.4 ± 0.4	−20.3 ± 0.4	8.1 ± 0.5	14.2 ± 0.3	4xu0
82		3.12	0.324 ± 0.023	−12.9 ± 0.9	−18.8 ± 0.0	5.9 ± 0.1	13.8 ± 0.8	4xu1
87		0.78	0.592 ± 0.009	−12.6 ± 0.1	−21.4 ± 0.5	8.8 ± 0.6	15.0 ± 1.0	4xu2
90		3.12	0.315 ± 0.003	−13.0 ± 0.1	−25.5 ± 0.7	12.6 ± 0.7	14.7 ± 0.3	4xu3

^aCompetitive ITC experiments to determine K_D and ΔG were performed at least in triplicate with 2 different enzyme batches while direct titration experiments were done in triplicate. All analogs showed n values of 1 ± 0.2.

^bMinimum inhibitory concentrations (MIC) that resulted in >90% growth inhibition of M. tuberculosis H37Rv were determined by a broth microdilution assay in GAS medium. Experiments were performed twice independently in triplicate. The MIC is defined as the lowest concentration of inhibitors that prevented growth, as determined by measuring the endpoint OD₆₀₀ values.

^cNot determined