Table 1 Kinetic parameters of ligand binding by Fc-fusion protein constructs as determined by SPR.
From: Functionally diverse heteromeric traps for ligands of the transforming growth factor-β superfamily
Ligand | Kinetic parameter | Reference | Heterodimers | Homodimers | ||||
|---|---|---|---|---|---|---|---|---|
IIB-Fc:IIB-Fc | IIB-Fc:ALK4-Fc | IIB-Fc:ALK7-Fc | IIB-Fc:ALK3-Fc | ALK4-Fc:ALK4-Fc | ALK7-Fc:ALK7-Fc | ALK3-Fc:ALK3-Fc | ||
Activin A | ka (× 106 M−1 s−1) | 7.8 ± 0.1 | 7.4 ± 1.0 | 20.0 ± 0.8 | 44.7 ± 0.9 | 0.2 ± 0.0 | NB | NB |
kd (× 10–6 s−1) | 84.5 ± 4.2 | 139 ± 34.3 | 8150 ± 266 | 7330 ± 327 | > 10,000 | |||
KD (pM) | 10.9 ± 0.5 | 18.4 ± 2.5 | 410 ± 28.5 | 164 ± 4.8 | > 10,000 | |||
Activin B | ka (× 106 M−1 s−1) | 5.7 ± 0.2 | 5.3 ± 0.3 | 7.4 ± 0.1 | 4.8 ± 0.2 | NB | NB | NB |
kd (× 10–6 s−1) | 21.9 ± 2.6 | 80.7 ± 10.3 | 114 ± 12.3 | 335 ± 7.8 | ||||
KD (pM) | 3.8 ± 0.4 | 15.3 ± 1.9 | 15.3 ± 1.4 | 69.6 ± 2.0 | ||||
GDF3 | ka (× 106 M−1 s−1) | 2.9 ± 0.1 | 1.1 ± 0.0 | 1.1 ± 0.0 | 0.9 ± 0.0 | NB | NB | NB |
kd (× 10–6 s−1) | 1880 ± 34.6 | > 10,000 | > 10,000 | > 10,000 | ||||
KD (pM) | 640 ± 6.7 | > 10,000 | > 10,000 | > 10,000 | ||||
GDF8 | ka (× 106 M−1 s−1) | 3.2 ± 0.1 | 2.8 ± 0.1 | 3.0 ± 0.1 | 2.7 ± 0.1 | NB | NB | NB |
kd (× 10–6 s−1) | 125 ± 3.3 | 236 ± 1.3 | 637 ± 2.9 | 696 ± 6.8 | ||||
KD (pM) | 39.1 ± 0.7 | 83.7 ± 2.0 | 212 ± 2.7 | 256 ± 6.9 | ||||
GDF11 | ka (× 106 M−1 s−1) | 19.4 ± 0.3 | 15.2 ± 0.3 | 13.5 ± 0.2 | 13.2 ± 0.3 | 0.5 ± 0.2 | NB | NB |
kd (× 10–6 s−1) | 75.6 ± 2.2 | 164 ± 3.2 | 642 ± 10.7 | 641 ± 2.4 | > 10,000 | |||
KD (pM) | 3.9 ± 0.2 | 10.8 ± 0.4 | 47.4 ± 0.0 | 48.5 ± 1.3 | > 10,000 | |||
BMP2 | ka (× 106 M−1 s−1) | 1.0 ± 0.0 | 0.4 ± 0.0 | 0.4 ± 0.0 | 12.3 ± 0.5 | NB | NB | 1.5 ± 0.0 |
kd (× 10–6 s−1) | > 10,000 | > 10,000 | > 10,000 | 35.5 ± 1.8 | 260 ± 12.1 | |||
KD (pM) | > 10,000 | > 100,000 | > 100,000 | 2.9 ± 0.3 | 177 ± 10.1 | |||
BMP4 | ka (× 106 M−1 s−1) | 0.6 ± 0.0 | NB | NB | 3.0 ± 0.0 | NB | NB | 0.4 ± 0.0 |
kd (× 10–6 s−1) | 3520 ± 193 | 12.6 ± 0.7 | 88.3 ± 4.9 | |||||
KD (pM) | 5430 ± 95.8 | 4.1 ± 0.2 | 202 ± 11.9 | |||||
BMP6 | ka (× 106 M−1 s−1) | 7.8 ± 0.1 | 7.6 ± 0.2 | 5.9 ± 0.5 | 4.6 ± 0.2 | NB | NB | 0.6 ± 0.0 |
kd (× 10–6 s−1) | 2730 ± 55.7 | 5730 ± 249 | 4240 ± 307 | 214 ± 11.0 | 5690 ± 128 | |||
KD (pM) | 348 ± 4.2 | 758 ± 15.2 | 715 ± 8.4 | 46.0 ± 1.6 | 9030 ± 58.3 | |||
BMP7 | ka (× 106 M−1 s−1) | 0.8 ± 0.0 | 0.8 ± 0.0 | 0.7 ± 0.0 | 11.9 ± 0.2 | NB | NB | NB |
kd (× 10–6 s−1) | > 10,000 | > 10,000 | > 10,000 | 1970 ± 50.2 | ||||
KD (pM) | > 10,000 | > 10,000 | > 10,000 | 165 ± 2.4 | ||||
BMP9 | ka (× 106 M−1 s−1) | 12.4 ± 0.7 | 8.9 ± 0.6 | 7.1 ± 0.9 | 9.7 ± 0.3 | NB | NB | NB |
kd (× 10–6 s−1) | 1100 ± 6.6 | > 10,000 | > 10,000 | > 10,000 | ||||
KD (pM) | 93.3 ± 4.3 | 1360 ± 77.9 | 2300 ± 145 | 1760 ± 30.5 | ||||
BMP10 | ka (× 106 M−1 s−1) | 18.6 ± 0.8 | 41.8 ± 0.3 | 44.5 ± 1.0 | 21.5 ± 0.1 | NB | NB | NB |
kd (× 10–6 s−1) | 121 ± 2.6 | 2800 ± 35.3 | 3140 ± 60.6 | 719 ± 11.0 | ||||
KD (pM) | 6.5 ± 0.4 | 67.0 ± 1.1 | 70.6 ± 1.0 | 33.5 ± 0.7 | ||||
