Table 1. In vitro activity of GLP-1R peptides.
| Peptide | Gαs | Gαq | β-Arrestin 1 | β-Arrestin 2 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Human GLP-1R |
Mouse GLP-1R |
Human GLP-1R |
Human GLP-1R |
Human GLP-1R |
||||||||
| EC50 (nM) | Emax (%) | EC50 (nM) | Emax (%) | EC50 (nM) | Emax (%) | EC50 (nM) | Emax (%) | EC50 (nM) | Emax (%) | |||
| Ex4 | 0.091±0.016 | 100±1 | 0.322±0.096 | 100±1 | 55.1±26 | 100±3 | 29.6±5 | 100±2 | 5.6±2 | 100±7 | ||
| GLP-1 | 0.912±0.141 | 73±4 | 0.623±0.176 | 89±5 | 308.5±91 | 60±8 | 280.8±86 | 71±9 | 60.1±12 | 77±7 | ||
| P1 | 2028±234 | 14±5 | 542±234 | 18±7 | ND | ND | ND | ND | ND | ND | ||
| P2 | 385.6±167 | 51±16 | 364.3±138 | 53±10 | ND | ND | ND | ND | ND | ND | ||
| P3 | NC | NC | NC | NC | ND | ND | ND | ND | ND | ND | ||
| P5 | 0.852±0.136 | 102±1 | 0.967±0.325 | 100±2 | 84.9±23 | 113±11 | 447.6±134 | 29±4 | 529.7±145 | 32±2 | ||
| P10 | 3.2±2.7 | 11±4 | NC | 5±3 | ND | ND | ND | ND | ND | ND | ||
Characterization of the relative efficacy of the peptide to signal through Gαs-protein in human and mouse GLP-1R expressing cell lines, and through Gαq-protein, β-arrestin 1 and -2 in human GLP-1R expressing cell lines. EC50 values represent the concentration (nM) of peptide required to stimulate half-maximum GLP-1R activation. Emax (%) values represent the maximum activation obtained with each peptide relative to Ex4 maximum activation. The data are means±s.d. of a typical experiment that was performed three times. Sequences can be found in Fig. 1e. NC, do not converge; ND, not determined.