Table 1.
Compounds and their potency measured using the cloned human GLP-1 receptor expressed in baby hamster kidney cells.
| Compound | Parent peptide | Acyl site | Acyl substituent | Potency (EC50, pM) |
|---|---|---|---|---|
| 1 | GLP-1(7-37) | None | 55 ± 19 | |
| 2 | K8R26, 34-GLP-1(7-37) | K8 | γ-Glu-C16 | 1260 ± 210 |
| 3 | K18R26, 34-GLP-1(7-37) | K18 | γ-Glu-C16 | 35.2 ± 6.2 |
| 4 | K23R26, 34-GLP-1(7-37) | K23 | γ-Glu-C16 | 30.1 ± 3.3 |
| 5 | R34-GLP-1(7-37) | K26 | γ-Glu-C16 | 61.0 ± 7.1 |
| 6 | K27R26, 34-GLP-1(7-37) | K27 | γ-Glu-C16 | 36.3 ± 0.3 |
| 7 | R26-GLP-1(7-37) | K34 | γ-Glu-C16 | 121 ± 26 |
| 8 | K36R26, 34-GLP-1(7-36) | K36 | γ-Glu-C16 | 36.4 ± 2.1 |
| 9 | R26, 34-GLP-1(7-38) | K38 | γ-Glu-C16 | 53.0 ± 2.8 |
| 10 | GLP-1(7-37) | K26, 34 | bis-C16-diacid | 7,000 ± 7 |
| 11 | GLP-1(7-37) | K26, 34 | bis-γ-Glu-C16 | 16,700 ± 3,700 |
| 12 | GLP-1(7-37) | K26, 34 | bis-γ-Glu-C14 | 3,050 ± 350 |
| 13 | GLP-1(7-37) | K26, 34 | bis-C12-diacid | 177 ± 52 |
| 14 | R34-GLP-1(7-37) | K26 | C16-diacid | 154 ± 66 |
| 15 | R34-GLP-1(7-37) | K26 | C14-diacid | 72 ± 0.7 |
| 16 | R34-GLP-1(7-37) | K26 | γ-Glu-C18 | 194 ± 24 |
| 17 | R34-GLP-1(7-37) | K26 | γ-Glu-C14 | 22.0 ± 7.1 |
| 18 | R34-GLP-1(7-37) | K26 | γ-Glu-C12 | 27.3 ± 8.4 |
| 19 | desamino-H7R34-GLP-1(7-37) | K26 | γ-Glu-C16 | 687 ± 129 |
| 20 | R34-GLP-1(7-37) | K26 | GABA-C16 | 84.4 ± 22.1 |
| 21 | R34-GLP-1(7-37) | K26 | β-Ala-C16 | 113 ± 3 |
| 22 | R34-GLP-1(7-37) | K26 | Iso-Nip-C16 | 410 ± 120 |
| 23 | desamino-H7R26-GLP-1(7-37) | K34 | γ-Glu-C16 | 2360 ± 370 |
| 24 | desamino-H7R26-GLP-1(7-37) | K34 | C8 | 236 ± 66 |
| 25 | desamino-H7R26-GLP-1(7-37) | K34 | γ-Glu-C8 | 169 ± 1 |
| 26 | K36R26, 34-GLP-1(7-36) | K36 | C20-diacid | 210 ± 14 |
| 27 | K36R26, 34-GLP-1(7-36) | K36 | C16-diacid | 7.89 ± 1.21 |
| 28 | K36R26, 34-GLP-1(7-36) | K36 | γ-Glu-C18 | 116 ± 3 |
| 29 | R26, 34-GLP-1(7-38) | K38 | C16-diacid | 5.60 ± 3.5 |
| 30 | R26, 34-GLP-1(7-38) | K38 | C12-diacid | 4.19 ± 0.98 |
| 31 | R26, 34-GLP-1(7-38) | K38 | γ-Glu-C18 | 115 ± 21 |
| 32 | R26, 34-GLP-1(7-38) | K38 | γ-Glu-C14 | 54 ± 1 |
| 33 | G8R26, 34-GLP-1(7-38) | K38 | γ-Glu-C16 | 328 ± 14 |
| 34 | E37R26, 34-GLP-1(7-38) | K38 | γ-Glu-C16 | 27.2 ± 0.1 |
| 35 | E37G8R26, 34-GLP-1(7-38) | K38 | γ-Glu-C16 | 135 ± 7 |
| 36 | E37G8R26, 34-GLP-1(7-38) | K38 | γ-Glu-C18 | 213 ± 30 |
Abbreviations used for acyl groups in lysine Nϵ-acylated peptides: γ-Glu-C8, γ-L-glutamoyl(Nα-octanoyl); γ-Glu-C14, γ-Lglutamoyl(Nα-tetradecanoyl); γ-Glu-C16, γ-L-glutamoyl(Nα-hexadecanoyl); γ-Glu-C18, γ-L-glutamoyl(Nα-octadecanoyl); C8, octanoyl; C12-diacid, ω-carboxyundecanoyl; C16-diacid, ω-carboxypentadecanoyl; C20-diacid, ω-carboxynonadecanoyl; GABA-C16, γ-aminobutyroyl(Nγ-hexadecanoyl); Iso-Nip-C16, 1-(hexadecanoyl)piperidyl-4-carboxy. Data are given as mean ± standard deviation of two individual experiments with triplicate samples. EC50, effective concentration. Source: Knudsen et al. (42).