Affinities of bombesin, neuromedin B, and various synthetic bombesin analogs with position 11 conformationally restricted substitutions for human BRS-3, GRP, and NMB receptors
Data are calculated from dose-inhibition curves in Figs 2, 3, 4. The affinities of [D-Tyr6,β-Ala11,Phe13,Nle14]Bn(6-14), Bn, and NMB were calculated by a least-squares curve-fitting program (LIGAND). The remaining affinities were calculated using the Cheng-Prusoff equation. All values are means ± S.E.M. from at least three experiments. The structures of these conformationally restricted analogs are shown in Fig. 1.
Peptide No. | Peptide Structure | Ki | ||||
|---|---|---|---|---|---|---|
| hBRS-3/Balb/c 3T3 Cells | hGRP-R/Balb/c 3T3 Cells | hNMB-R/Balb/c 3T3 Cells | ||||
| nM | ||||||
| 1 | [d-Tyr6,β-Ala11,Phe13,Nle14]Bn(6-14) | 0.82 ± 0.1 | 0.5 ± 0.04 | 5.9 ± 0.4 | ||
| 2 | [d-Tyr6,(R)-Apa11,Phe13,Nle14]Bn(6-14) | 2.8 ± 0.1 | 151 ± 6 | 2400 ± 96 | ||
| 3 | [d-Tyr6,(S)-Apa11,Phe13,Nle14]Bn(6-14) | 8.2 ± 1.1 | 110 ± 5 | 4370 ± 150 | ||
| 4 | [d-Tyr6,(S)-Apa11-2Cl,Phe13,Nle14]Bn(6-14) | 85 ± 7 | 398 ± 28 | 5890 ± 385 | ||
| 5 | [d-Tyr6,(R)-Apa11-2Cl,Phe13,Nle14]Bn(6-14) | 24 ± 1 | 229 ± 28 | 6920 ± 350 | ||
| 6 | [d-Tyr6,(S)-Apa11-4Cl,Phe13,Nle14]Bn(6-14) | 776 ± 134 | 741 ± 85 | 1950 ± 337 | ||
| 7 | [d-Tyr6,(R)-Apa11-4Cl,Phe13,Nle14]Bn(6-14) | 8.2 ± 1.1 | 1860 ± 69 | 7200 ± 840 | ||
| 8 | [d-Tyr6,(S)-Apa11-3Cl,Phe13,Nle14]Bn(6-14) | 15.8 ± 1.1 | 110 ± 17 | 831 ± 192 | ||
| 9 | [d-Tyr6,(R)-Apa11-3Cl,Phe13,Nle14]Bn(6-14) | 107 ± 4 | 2510 ± 290 | > 10,000 | ||
| 10 | [d-Tyr6,β-Asp11,Phe13,Nle14]Bn(6-14) | 490 ± 50 | 396 ± 44 | 427 ± 54 | ||
| 11 | [d-Tyr6,β-Asp(BzlAmd)11,Phe13,Nle14]Bn(6-14) | 708 ± 61 | 397 ± 51 | 646 ± 59 | ||
| 12 | [d-Tyr6,β-Dap11,Phe13,Nle14]Bn(6-14) | 2.3 ± 0.1 | 1.0 ± 0.1 | 43 ± 5 | ||
| 13 | [d-Tyr6,Nα-acetyl-Dap11,Phe13,Nle14]Bn(6-14) | 15.8 ± 2.9 | 1.7 ± 0.2 | 89 ± 4 | ||
| 14 | [d-Tyr6,Nα-benzoyl-Dap11,Phe13,Nle14]Bn(6-14) | 12.3 ± 1.3 | 3.1 ± 0.5 | 55 ± 3 | ||
| 15 | [d-Tyr6,β-Ala11,Phe13,β-Dap(Pr)14]Bn(6-14) | 2400 ± 138 | 85 ± 17 | > 10,000 | ||
| Bn | Bombesin | > 10,000 | 0.36 ± 0.07 | 22 ± 0.9 | ||
| NMB | Neuromedin B | > 10,000 | 97 ± 11 | 0.55 ± 0.03 | ||