Table 4.

Inhibition constants for optimal vinyl sulfone inhibitors

Inhibitor Name	DPAP3			DPAP1			CatC			Specificity ratioa
	k inact ·103 (s−1)	K i (nm)	k inact/K i ·10−3 (m −1·s−1)	k inact ·103 (s−1)	K i (nm)	k inact/K i ·10−3 (m −1·s−1)	k inact ·103 (s−1)	K i (nm)	k inact/K i ·10−3 (m −1·s−1)	DPAP1/DPAP3	DPAP1/CatC	DPAP3/CatC
Pro‐hPhe‐VS	3.5 ± 0.2	860 ± 100	4.1 ± 0.3	2.1 ± 0.2	4.6 ± 0.7	470 ± 35	1.45 ± 0.07	34 ± 5	42 ± 5	115	11	0.10
hPro‐hPhe‐VS	2.1 ± 0.1	30 ± 7	69 ± 13	4.8 ± 0.6	3.9 ± 1.5	1230 ± 400	1.67 ± 0.08	22 ± 3	76 ± 0.8	18	16	0.91
hPro‐nLeu(o‐Bzl)‐VS	2.0 ± 0.1	39 ± 6	53 ± 6.5	2.9 ± 0.3	0.8 ± 0.2	3560 ± 150	1.67 ± 0.03	11.2 ± 0.6	150 ± 6	68	24	0.35
Tyr(NO2)‐hPhe‐VS	2.26 ± 0.05	2.4 ± 0.2	950 ± 74	3.8 ± 1	25 000 ± 1400	0.15 ± 0.05	3.2 ± 0.6	58 000 ± 20 000	0.054 ± 0.008	0.00016	2.8	17 600
Tyr(NO2)‐nLeu(o‐Bzl)‐VS	2.7 ± 0.2	53 ± 10	51 ± 10	2.6 ± 0.3	2400 ± 900	1.1 ± 0.3	2.9 ± 0.2	7700 ± 1400	0.38 ± 0.05	0.032	2.9	89
2Nal‐hPhe‐VS	2.59 ± 0.07	254 ± 16	10.2 ± 0.5	6.7 ± 0.2	33 000 ± 2000	0.2 ± 0.005	3.7 ± 0.2	4000 ± 700	0.9 ± 0.1	0.02	0.22	11
2Nal‐nLeu(o‐Bzl)‐VS	6.0 ± 0.7	2800 ± 600	2.2 ± 0.3	5.0 ± 1.7	27 000 ± 16 000	0.19 ± 0.05	2.4 ± 0.6	1740 ± 140	1.37 ± 0.09	0.14	0.14	1.0
Igl‐hPhe‐VS	2.1 ± 0.7	10 ± 1	205 ± 22	2.7 ± 0.1	5400 ± 500	0.50 ± 0.03	5.8 ± 0.3	320 ± 70	18 ± 3	0.0024	0.028	11.4
Igl‐nLeu(o‐Bzl)‐VS	5.6 ± 0.4	160 ± 30	35 ± 4.5	4.1 ± 0.2	4800 ± 500	0.86 ± 0.05	1.48 ± 0.06	11 ± 2	135 ± 14	0.037	0.0064	0.17
L‐Trp‐hPG‐VS	3 ± 1	330 ± 150	9.1 ± 1.5	2.1 ± 0.2	2800 ± 450	0.74 ± 0.07	1.73 ± 0.03	28 ± 2	61 ± 4	0.12	0.012	0.10
L‐Trp‐hPhe‐VS	3.3 ± 0.4	65 ± 15	52 ± 7	1.7 ± 0.1	540 ± 80	3.20 ± 0.3	2.2 ± 0.09	16 ± 3	131 ± 15	0.094	0.024	0.26
L‐Trp‐nLeu(o‐Bzl)‐VS	3.2 ± 0.3	4 ± 1	826 ± 193	2.2 ± 0.1	380 ± 60	5.8 ± 0.6	1.74 ± 0.03	4.9 ± 0.3	355 ± 18	0.0070	0.016	2.3
D‐Trp‐hPhe‐VS	1.7 ± 0.6	5500 ± 3000	0.32 ± 0.08	2.7 ± 0.2	105 000 ± 10 000	0.026 ± 0.001	2.6 ± 0.1	4200 ± 600	0.62 ± 0.07	0.12	0.042	0.34
D‐Trp‐nLeu(o‐Bzl)‐VS	3.6 ± 0.2	7600 ± 600	0.47 ± 0.01	5.5 ± 0.7	127 000 ± 20 000	0.044 ± 0.002	1.97 ± 0.06	1100 ± 100	1.7 ± 0.1	0.094	0.026	0.28
nVal‐hPhe‐VS	2.6 ± 0.4	2.8 ± 0.9	940 ± 160	2.0 ± 0.1	0.6 ± 0.2	3160 ± 750	2.2 ± 0.1	0.38 ± 0.08	5830 ± 970	3.36	0.54	0.16

^aSpecificity ratio was calculated based on k _inact/K _i values; numbers highlighted in bold indicate more than 100‐fold selectivity for the indicated enzymes. Standard error of the global fit for each parameter and inhibitor obtained by fitting k _obs values (single replicate) to Eqs. 6 or 7 are shown.