Table 2 Kinetic characterization of back mutants and combinatorial mutagenesis
Name | Second order rate constant (k2) versus Pka (x105 M− 1s− 1) | Second order rate constant (k2) versus FXIa (x105 M− 1s− 1) | Selectivity (Pka k2: FXIa k2) | Stoichiometry of inhibition (SI) for Pka | Stoichiometry of inhibition (SI) for FXIa |
|---|---|---|---|---|---|
AAT M358R | 0.394 ± 0.019 | 2.18 ± 0.084 | 0.181 | 3.18 ± 0.10 | 3.48 ± 0.36 |
7-FLIPS-3 | 0.620 ± 0.035 *** | 0.244 ± 0.011 **** | 2.54 | 5.78 ± 0.31**** | 185 ± 9.2**** |
7-FLEPS-3 | 1.76 ± 0.13 *** | 1.06 ± 0.14 **** | 1.66 | 3.18 ± 0.085 | 87.7 ± 1.0**** |
7-FLEAS-3 | 1.33 ± 0.081 **** | 3.24 ± 0.18 *** | 0.410 | 1.79 ± 0.035**** | 1.49 ± 0.028** |
2-PRRAY-3ʹ | 0.0400 ± 0.0071 **** | 0.020 ± 0.01 **** | 2.00 | 19.9 ± 2.4*** | 28.8 ± 8.2** |
2-PRSAY-3ʹ | 0.0380 ± 0.0045 **** | 0.060 ± 0.01 **** | 0.633 | 16.9 ± 1.9*** | 14.2 ± 0.84**** |
2-PRSIY-3ʹ | 0.0720 ± 0.0045 **** | 0.096 ± 0.006 **** | 0.750 | 11.2 ± 0.54**** | 9.44 ± 0.24**** |
7-QLIPSVRRAY-3ʹ | 0.164 ± 0.0055 **** | ND | ND | 10.7 ± 0.14**** | 3110 ± 290**** |