Table 4.
IC50 Values for PeIA Analogs with Single Substitutions of His9, Val10, Glu14, and Leu15 a
|
α3β2 nAChR |
α6/α3β2β3 nAChR |
||||||
|---|---|---|---|---|---|---|---|
| peptide | IC50 (nM) | n | log change in IC50 | IC50 (nM) | n | log change in IC50 | selectivity ratio |
| PeIA | 19.4 (15.3–24.6) | 5 | 19.8 (17.9–21.8) | 4 | 1 | ||
| [His9]PeIA | 1.30 (1.19–1.41) | 4 | −1.2 | 0.99 (0.93–1.05)12 | 4 | −1.3 | 1 |
| [Asn9]PeIA | 9.32 (8.32–10.4) | 6 | −0.3 | 16.0 (12.8–20.0) | 4 | −0.1 | 2 |
| [Tyr9]PeIA | 9.18 (7.67–11.0) | 5 | −0.3 | 13.0 (9.0–18.9) | 4 | −0.2 | 1 |
| [Thr9]PeIA | 7.10 (5.78–8.72) | 5 | −0.4 | 5.12 (4.51–5.81) | 4 | −0.6 | 1 |
| [Ala10]PeIA | 3.37 (3.05–3.72) | 4 | −0.8 | 2.4 (2.0–2.7)12 | −0.9 | 1 | |
| [Ile10]PeIA | 11.8 (10.2–13.6) | 4 | −0.2 | 13.4 (10.9–16.6) | 6 | −0.2 | 1 |
| [Leu10]PeIA | 10.6 (9.2–12.2) | 4 | −0.3 | 18.8 (16.0–22.1)13 | 0.1 | 2 | |
| [Nle10]PeIA | 9.29 (7.99–10.8) | 6 | −0.3 | 19.9 (17.3–23.0) | 4 | 0.1 | 2 |
| [Thr10]PeIA | 24.5 (21.7–27.8) | 5 | 0.1 | 29.0 (23.7–36.2) | 4 | 0.2 | 1 |
| [Gla14]PeIA | 16.6 (15.1–18.4) | 4 | −0.1 | 28.5 (25.7–31.6) | 4 | 0.2 | 2 |
| [Asp14]PeIA | 65.1 (44.9–94.4) | 4 | 0.5 | 21.0 (16.6–26.5) | 4 | 0.1 | 0.3 |
| [Adi14]PeIA | 115 (88.9–148) | 4 | 0.8 | 29.2 (24.3–35.2) | 5 | 0.2 | 0.3 |
| [Asu14]PeIA | 155 (123–196) | 4 | 0.9 | 135 (107–171) | 4 | 0.8 | 1 |
| [Gln14]PeIA | 77.1 (57.8–1028) | 5 | 0.6 | 14.4 (11.7–17.6) | 5 | −0.1 | 0.2 |
| [Arg14]PeIA | 109 (83.9–141) | 4 | 0.7 | 7.40 (6.06–9.04) | 4 | −0.4 | 0.1 |
| [Arg15]PeIA | 161 (133–196) | 4 | 0.9 | 54.0 (33.1–88.1) | 4 | 0.4 | 0.3 |
| [Ala15]PeIA | 733 (522–1028) | 4 | 1.6 | 82.5 (63.5–107)13 | 0.6 | 0.1 | |
| [Val15]PeIA | 40.9 (32.8–50.9) | 6 | 0.3 | 5.20 (4.40–6.14) | 4 | −0.6 | 0.1 |
| [Ile15]PeIA | 6.41 (5.51–7.46) | 4 | −0.5 | 12.8 (10.5–15.5) | 5 | −0.2 | 2 |
| [Nle15]PeIA | 21.1 (18.5–24.1) | 4 | 0.1 | 13.2 (10.9–15.9) | 5 | −0.2 | 0.6 |
a
Values in parentheses indicate the 95% CI of the IC50 values. Changes in potency were calculated as the log(analog IC50)/(PeIA IC50), negative values indicate increased potency and positive values indicate decreased potency. Selectivity was calculated as the IC50 ratio of (α6/α3β2β3)/(α3β2).