TABLE 2.

Substrate kinetics and compound 3 inhibition

Substrate and inhibitor steady state kinetic studies were performed using the indicated enzyme and nucleic acid substrate. AMP formed was determined as a function of time from 20-min progress curves conducted in triplicate, and Equation 4 was fit to the initial rates to determine k_cat and K_m values, or Equation 5 was fit to determine K_i values for compound 3. The best fit parameter estimates are shown ± the standard error of the fit.

	2–5A			OligoA-12			Compound 3, Ki
	Km	kcat	kcat/Km	Km	kcat	kcat/Km
	μm	s−1	m−1 s−1	μm	s−1	m−1 s−1	nm
PDE12	103 ± 4	27 ± 0.5	2.6 × 105	280 ± 100	11 ± 3	0.39 × 105	17.5 ± 0.8
CNOT6	45 ± 7	6 ± 0.3	1.3 × 105	164 ± 86	2.6 ± 0.7	0.16 × 105	>10,000