Table 1. Pharmacological Data of Helianorphins at the KORa.
| affinity | potency/efficacy cAMP | |||
|---|---|---|---|---|
| ligand | sequence* | Ki ± SD (M) | EC50 ± SD (M) | Emax ± SD (%) |
| dyn A 1–13 | YGGFLRRIRPKLK-NH2 | 3.1 ± 0.3 × 10–10 | 2.8 ± 0.7 × 10–9 | 100 |
| SFTI-1 | c-CTKSIPPICFPDGR | >3.0 × 10–5 | n.d. | n.d. |
| helianorphin-1 | c-CYGGFLRRIRPKLKCFPDGR | 2.2 ± 0.6 × 10–7 | 1.7 ± 0.1 × 10–6 | 106 ± 8.4 |
| helianorphin-2 | c-CTKSIPPICYGGFLRRIRPKLK | 9.7 ± 0.5 × 10–8 | 1.3 ± 0.4 × 10–6 | 102 ± 10 |
| helianorphin-3 | c-CYGGFLRRICFPDGR | 3.2 ± 0.4 × 10–6 | 1.4 ± 0.3 × 10–6 | 85.1 ± 1.8 |
| helianorphin-4 | c-CTKSIPPICYGGFLRRI | 2.5 ± 0.05 × 10–6 | 4.7 ± 1.3 × 10–6 | 87.8 ± 33 |
| helianorphin-5 | c-CYGGFLRICFPDGR | >10–5 | n.d. | n.d. |
| helianorphin-6 | c-CTYGGFLRCFPDGR | >10–5 | n.d. | n.d. |
| helianorphin-7 | c-CTASIPPICYGGFLR | >10–5 | n.d. | n.d. |
| helianorphin-8 | c-CTYGGFPICFPDGR | >10–5 | n.d. | n.d. |
| helianorphin-9 | c-CTASIPPICYGGFR | >10–5 | n.d. | n.d. |
| helianorphin-10 | c-CTfflkPICFPDGR | >10–5 | n.d. | n.d. |
| helianorphin-11 | c-CTASIPPICfflkR | >10–5 | n.d. | n.d. |
| helianorphin-12 | c-CTffbrPICFPDGR | 2.3 ± 0.5 × 10–6 | 1.5 ± 0.3 × 10–6 | 117 ± 12 |
| helianorphin-13 | c-CTASIPPICffbrR | >10–5 | n.d. | n.d. |
| helianorphin-14 | c-CYGGFLRRIRpKLKCFPDGR | 2.2 ± 0.3 × 10–7 | n.d. | n.d. |
| helianorphin-15 | c-CffbrLRRIRPKLKCFPDGR | 1.7 ± 0.1 × 10–7 | n.d. | n.d. |
| helianorphin-16 | c-CTASIPPICffbrLRRIRPKLK | 2.5 ± 0.2 × 10–7 | n.d. | n.d. |
| helianorphin-17 | c-CTASIPPICffbrLRRIRpKLK | 1.2 ± 0.5 × 10–7 | n.d. | n.d. |
| helianorphin-18 | c-CTYGGFLRCRIRPKLK | 6.5 ± 1.5 × 10–7 | n.d. | n.d. |
| helianorphin-19 | c-CYGGFLRRCIRPKLK | 2.1 ± 0.8 × 10–8 | 4.5 ± 0.6 × 10–8 | 108 ± 11 |
a
Data are from three to six independent biological replicates. *Grafted epitopes are underlined; lysine (K) was replaced with alanine (A) to abolish trypsin inhibitory activity and is shown in the italic font; f, l, k, b, and r denote D-enantiomers of phenylalanine, leucine, lysine, norleucine, and arginine, respectively. n.d., not determined; dyn A, dynorphin A; and SFTI, sunflower trypsin inhibitor.