TABLE 1.
PNA5 peptide characteristics
Compares physiochemical and PK characteristics of PNA5 to those observed with Ang-(1-7).
| Parameter | PNA5 Activity | Ang-(1-7) Activity | Comparisons |
|---|---|---|---|
| Molecular wt. | 1278 g/mol | 898 g/mol | Glucose adds 275 g/mol |
| Solid stability | >1 yr @ RT | >1 yr @ RT | PNA5 = Ang-(1-7) |
| Aqueous stability | >6 mo @ RT | >6 mo @ RT | PNA5 = Ang-(1-7) |
| Aqueous solubility | 20 mg/ml | 20 mg/ml | PNA5 = Ang-(1-7) |
| In vitro t1/2 | t1/2 = 1.06 ± 0.20 h | t1/2 = 0.25 ± 0.05 h | PNA5 400% ↑ Ang-(1-7) |
| In vivo Cmax serum dose 10 mg/kg, s.c. | 6208.0 ± 4883 ng/ml (n = 8) | 917.8 ± 451 ng/ml | ↑ PNA5 2.6 log fold greater than Ang-(1-7) |
| In vivo Cmax CSF dose 10 mg/kg, s.c. | 422.8 ± 313 ng/ml | 221.8 ± 112 ng/ml | ↑ PNA5 2.6 log fold greater than Ang-(1-7) |
| In vivo AUC serum dose 10 mg/kg, s.c. | 14,609.6 ± 7425 ng ml/min (n = 8) | 5732.5 ± 2034 ng ml/min (n = 8) | PNA5 338% ↑ Ang-(1-7P) |
| In vivo AUC CSF dose 10 mg/kg, s.c. | 6141.3 ± 3616 ng ml/min | 2794.1 ± 1369 | PNA5 219% ↑ Ang-(1-7) |
| In vivo t1/2 serum dose 10 mg/kg, s.c. | 18.2 ± 3 min | 20.9 ± 0.7 | PNA5 = Ang-(1-7) |
| In vivo t1/2 CSF dose 10 mg/kg, s.c. | 26.6 ± 3.6 | 24.7 ± 5 | PNA5 = Ang-(1-7) |
| In vitro bioactivity ROS inhibition | Potency IC50 = 0.1 μM | ||
| Cognitive protection NOR test/MWM spatial test dose 1 mg/kg per day, s.c., 21 days | PNA5 Improves NOR and MWM by >2 SDs compared with placebo | Ang-(1-7) improves NOR and MWM by >2 SDs compared with placebo (previously published data) | PNA5 = Ang-(1-7) |
RT, room temperature.