Table 1.
Binding of GLP-2 and teduglutide with GLP-2R mutantsa.
| Human GLP-2 (1–33) | Teduglutide | |||
|---|---|---|---|---|
| Receptor mutant | pIC50 | % Binding of WTb | pIC50 | % Binding of WT |
| WT (1–553) | 8.5 ± 0.07 | 99.2 ± 2.3 | 8.8 ± 0.05 | 99.7 ± 1.9 |
| Y1821.43A | 9.1 ± 1.2 | 3.4 ± 1.0*** | 9.2 ± 0.8 | 3.2 ± 1.3*** |
| Y1861.47A | N.B.c | N.B. | N.B. | N.B. |
| K2312.67A | N.B. | N.B. | N.B. | N.B. |
| R242ECL1E | N.B. | N.B. | N.B. | N.B. |
| R242ECL1A | 8.0 ± 0.5 | 4.2 ± 0.6*** | 8.7 ± 0.8 | 5.1 ± 1.5*** |
| D244ECL1A | 8.6 ± 0.2 | 69.1 ± 4.9*** | 9.0 ± 0.2 | 77.5 ± 5.7*** |
| N247ECL1A | 8.2 ± 0.1 | 130.7 ± 4.5*** | 8.6 ± 0.1 | 135.2 ± 4.4*** |
| W249ECL1A | 9.0 ± 1.2 | 2.2 ± 1.2*** | 8.8 ± 1.7 | 2.9 ± 2.0*** |
| Y252ECL1A | 8.4 ± 0.8 | 8.3 ± 1.8*** | 9.0 ± 0.6 | 6.3 ± 1.7*** |
| H2683.37A | 8.0 ± 1.4 | 2.1 ± 0.8*** | 9.7 ± 3.2 | 0.7 ± 1.8*** |
| N334ECL2 A | 9.5 ± 1.8 | 2.4 ± 1.3*** | 9.7 ± 2.7 | 2.0 ± 2.1*** |
| W3405.36A | 7.1 ± 0.4 | 7.3 ± 0.6*** | 8.8 ± 0.7 | 8.6 ± 1.8*** |
| R3445.40A | 8.6 ± 0.5 | 5.0 ± 0.8*** | 9.3 ± 0.6 | 3.5 ± 0.8*** |
| K4147.35 A | 8.5 ± 0.2 | 15.2 ± 1.0*** | 8.7 ± 0.2 | 13.9 ± 0.8*** |
| ECL1 (GLP-1R)d | 8.9 ± 1.7 | 3.4 ± 1.3*** | 7.8 ± 0.7 | 1.2 ± 0.5*** |
| ECL1 (poly-alanine)d | 8.2 ± 1.3 | 3.0 ± 1.1*** | N.B. | N.B. |
***P < 0.001.
aAll data were fitted with a three-parameter logistic curve to obtain pIC50 values. Data represent means ± SEM of at least three independent experiments performed in duplicate. One-way ANOVA and Dunnett’s post hoc tests were used to determine statistical differences.
bWT wild-type.
cN.B. no binding of the radioligand.
dGLP-2R mutants with ECL1 (residues 236–257) substituted by the corresponding segment of GLP-1R or poly-alanine are labeled as ECL1 (GLP-1R) and ECL1 (poly-alanine), respectively.