Structures and biological properties of ghrelin analogs
Xxx-Ser-Yyy-Zzz-Leu-Ser-Pro-Glu-His-Gln-His-Gln-Lys-Ala-Gln-Gln-Arg-Lys-Glu-Ser-Lys-Lys-Pro-Pro-Ala-Lys-Leu-Gln-Pro-Arg. Mean ± S.E.M. of at least three separate experiments. Ki was calculated using the Cheng-Prusoff equation (Cheng and Prusoff, 1973) (Kd = 0.44 ± 0.12 nM from the saturation binding experiment). For the calculation of ED50 ± S.E.M., food intake 250 min after the subcutaneous administration of analogs in doses of 0.1 to 10 mg/kg (maximal effect) was examined. n = 5–6 mice per group.
| No. | Compound | No. aa | Xxx | Yyy | Zzz | Binding Assay ([125I]ghr displacement) Ki | Orexigenic Effect ED50 |
|---|---|---|---|---|---|---|---|
| M | mg/kg | ||||||
| 1 | Ghrelin | 28 | Gly | Ser(O-oct) | Phe | (3.67 ± 1.05) × 10−9 | 2.39 ± 1.07 |
| 2 | [Dpr3]ghr | 28 | Gly | Dpr(N-oct) | Phe | (3.28 ± 1.03) × 10−9 | 0.82 ± 0.37 |
| 3 | [Sar1,Dpr3]ghr | 28 | Sar | Dpr(N-oct) | Phe | (2.56 ± 1.64) × 10−9 | 0.65 ± 0.29 |
| 4 | [Dpr3,Nal4]ghr | 28 | Gly | Dpr(N-oct) | Nal | (4.89 ± 0.94) × 10−10 | 1.13 ± 0.51 |
| 5 | [Sar1,Dpr3,Nal4]ghr | 28 | Sar | Dpr(N-oct) | Nal | (3.22 ± 1.15) × 10−10 | 1.27 ± 0.57 |
| 6 | [Dpr3,Cha4]ghr | 28 | Gly | Dpr(N-oct) | Cha | (1.67 ± 0.31) × 10−9 | 0.35 ± 0.16 |
| 7 | [Sar1,Dpr3,Cha4]ghr | 28 | Sar | Dpr(N-oct) | Cha | (2.70 ± 1.42) × 10−9 | 4.63 ± 2.07 |
| 8 | Ghr(1–5) | 5 | Gly | Ser(O-oct) | Phe | (1.83 ± 1.16) × 10−6 | No effect |
| 9 | [Dpr3]ghr(1–5) | 5 | Gly | Dpr(N-oct) | Phe | (1.93 ± 0.65) × 10−6 | No effect |
| 10 | [Sar1,Dpr3]ghr(1–5) | 5 | Sar | Dpr(N-oct) | Phe | NT | No effect |
| 11 | [Dpr3]ghr(1–8) | 8 | Gly | Dpr(N-oct) | Phe | NT | No effect |
| 12 | [Sar1,Dpr3]ghr(1–8) | 8 | Sar | Dpr(N-oct) | Phe | (3.24 ± 1.68) × 10−6 | No effect |
| 13 | [Trp3]ghr(1–5) | 5 | Gly | Trp | Phe | >10−5 | No effect |
| 14 | [Nal3]ghr(1–5) | 5 | Gly | Nal | Phe | >10−5 | No effect |
| 15 | desoct ghr | 28 | Gly | Ser | Phe | >10−5 | No effect |
| 16 | desoct [Dpr3]ghr | 28 | Gly | Dpr | Phe | >10−5 | No effect |
NT, not tested.