Table 3.
Pharmacokinetic effects of increased and α‐2,6‐siaylation
Construct | Signal sequence | Catalytic domain | Nuclease domain | Fc domain | Half‐life, hours | AUC, mOD/min hour |
---|---|---|---|---|---|---|
770 | 37 | 3,381 | ||||
1 | E592N | 40 | 1,935 | |||
2 | K369N/I371T | 35 | 2,561 | |||
2(ST) | K369N/I371T | 36 | 4,426 | |||
9 | V29N | S766N | H1064K N1065F | 65 | 6,047 | |
10 | C25N K27T | S766N | H1064K N1065F | 55 | 7,735 | |
1(ST) | E592N | 49 | 8,379 | |||
15(ST) | V29N | E592N | H1064K N1065F | 88 | 13,871 | |
13 | V29N | E592N | M883Y S885T T887E | 70 | 14,978 | |
9(ST) | V29N | S766N | H1064K N1065F | 86 | 15,099 | |
18 | E592N | M883Y S885T T887E | 83 | 19,638 | ||
14 | M883Y S885T T887E | 96 | 20,360 | |||
10(ST) | C25N K27T | S766N | H1064K N1065F | 70.1 | 18,207 | |
15 | V29N | E592N | H1064K N1065F | 99 | 22,620 | |
14(ST) | M883Y S885T T887E | 119 | 22,793 | |||
9(ST) A | V29N | S766N | H1064K N1065F | 115 | 26,312 | |
18(ST) | E592N | M883Y S885T T887E | 97.5 | 14,263 | ||
7 | I256T | 67 | 26,598 | |||
17 | V29N | I256T | P534N, V536T | M883Y S885T T887E | 120 | 33,752 |
19(ST) | I256T | M883Y S885T T887E | 170 | 35,252 | ||
17(ST) | V29N | I256T | P534N, V536T | M883Y S885T T887E | 205 | 36,595 |
19(ST) A | I256T | M883Y S885T T887E | 204 | 44,742 |
The color shades correspond to the domain coloring of the ENPP1 cartoon presented in Figure 1a, i.e., the listed mutations in the table are colored according to their domain location in the cartoon in figure 1a.
AUC, area under the curve; mOD, measured as the optical density.