Table 1.
Receptor binding affinities of human insulin, IGF-1, IGF-2, and insulin analogs
The Kd values were obtained from at least three measurements. n is the number of replicates. Asterisks indicate that binding of the ligand to a particular receptor differs significantly from that of insulin (*, p < 0.05; **, p < 0.01; ***, p < 0.001).
| Analog | IR-A |
IR-B |
IGF-1R |
|||
|---|---|---|---|---|---|---|
| Kd ± S.D. (n) | Relativea binding affinity | Kd ± S.D. (n) | Relativea binding affinity | Kd ± S.D. (n) | Relativea binding affinity | |
| nm | % | nm | % | nm | % | |
| Insulinb | 0.36 ± 0.14# (5) | 100 | 0.55 ± 0.27# (4) | 100 | 292 ± 54.30€ (3) | 0.08 |
| 0.45 ± 0.11$ (6) | 0.37 ± 0.11$ (4) | |||||
| 0.27 ± 0.02∧ (5) | 0.39 ± 0.14∧ (4) | |||||
| 0.25 ± 0.05≈ (5) | 0.55 ± 0.11€ (6) | |||||
| 0.35 ± 0.06€ (4) | ||||||
| IGF-1b | 31.50 ± 5.63# (4)*** | 1.1 | 223.9 ± 32.9# (4)*** | 0.2 | 0.25 ± 0.03# (4) | 100 |
| 0.11 ± 0.05$ (5) | ||||||
| 0.12 ± 0.02∧ (5) | ||||||
| 0.24 ± 0.10€ (5) | ||||||
| IGF-2 | 2.92 ± 0.24≈ (3)*** | 8.4 | 35.45 ± 11.22# (4)*** | 1.6 | 2.32 ± 1.24# (3)*** | 10.7 |
| [d-HisB24]-DTI-NH2 | 0.18 ± 0.02# (3) | 204 | 0.30 ± 0.15# (4) | 183 | 288 ± 18.61# (3) | 0.09 |
| [d-HisB24]-insulin | 0.126 ± 0.015€ (3)** | 280 | 0.22 ± 0.05€ (3)** | 251 | 24.41 ± 10.59# (3)** | 1.02 |
| Des-PheB24-insulin | 0.12 ± 0.01# (4)* | 305 | 0.42 ± 0.11# (4) | 132 | 77.82 ± 20.71# (3)** | 0.32 |
| [TyrB25, PheB26, AsnB27, LysB28, ProB29]-insulin | 0.31 ± 0.07∧ (3) | 86 | 0.53 ± 0.21∧ (3) | 75 | 143.60 ± 54.67∧ (5) | 0.08 |
| [TyrB25, PheB26, AsnB27, LysB28, ProB29, GlyB31, TyrB32]-insulin | 0.21 ± 0.06∧ (3) | 131 | 0.19 ± 0.03∧ (3) | 207 | 16.01 ± 6.24∧ (5)*** | 0.77 |
| [GlyB31, TyrB32]-insulin | 0.17 ± 0.07∧ (3)* | 162 | 0.13 ± 0.05∧ (3)* | 310 | 45.66 ± 17.72∧ (4)** | 0.27 |
| [d-HisB24, GlyB31, TyrB32]-insulin | 0.18 ± 0.02$ (3)** | 251 | 0.12 ± 0.03$ (3)* | 338 | 0.89 ± 0.20$ (6)*** | 12.4 |
a Relative binding affinity is defined as (Kd of human insulin or IGF-1/Kd of analog) × 100 (%).
b The Kd of human insulin for IR-A was determined in five independent measurements (#, $, ∧, ≈, and €) and for IR-B in four measurements (#, $, ∧, and €), and Kd of human IGF-1 for IGF-1R was determined in four measurements (#, $, ∧, and €). The individual values of Kd of a particular ligand are relative to a corresponding insulin or IGF-1 Kd values (e.g. # to #, etc.).