TABLE 1

PNA5 peptide characteristics

Compares physiochemical and PK characteristics of PNA5 to those observed with Ang-(1-7).

ParameterPNA5 ActivityAng-(1-7) ActivityComparisons
Molecular wt.1278 g/mol898 g/molGlucose adds 275 g/mol
Solid stability>1 yr @ RT>1 yr @ RTPNA5 = Ang-(1-7)
Aqueous stability>6 mo @ RT>6 mo @ RTPNA5 = Ang-(1-7)
Aqueous solubility20 mg/ml20 mg/mlPNA5 = Ang-(1-7)
In vitro t1/2t1/2 = 1.06 ± 0.20 ht1/2 = 0.25 ± 0.05 hPNA5 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/ml221.8 ± 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/min2794.1 ± 1369PNA5 219% ↑ Ang-(1-7)
In vivo t1/2 serum dose 10 mg/kg, s.c.18.2 ± 3 min20.9 ± 0.7PNA5 = Ang-(1-7)
In vivo t1/2 CSF dose 10 mg/kg, s.c.26.6 ± 3.624.7 ± 5PNA5 = Ang-(1-7)
In vitro bioactivity ROS inhibitionPotency IC50 = 0.1 μM
Cognitive protection NOR test/MWM spatial test dose 1 mg/kg per day, s.c., 21 daysPNA5 Improves NOR and MWM by >2 SDs compared with placeboAng-(1-7) improves NOR and MWM by >2 SDs compared with placebo (previously published data)PNA5 = Ang-(1-7)
  • RT, room temperature.