Table 2.
Potencya, subtype selectivity and maximum inhibitionb for the fourth generation of PnCS1 MAPS peptide analogues across NaV subtypes assessed using two-electrode voltage-clamp electrophysiology.
| Peptide | NaV1.2 | NaV1.4 | NaV1.5 | NaV1.6 | NaV1.8 |
|---|---|---|---|---|---|
|
| |||||
| PnCS1 | 1.0 ± 0.3 (97) | 0.6 ± 0.3 (94) | 2.8 ± 0.5 (94) | 0.7 ± 0.3 (96) | >100 (0) |
| PnCS1[R2A] | 2.9 ± 0.5a (84)b | 1.4 ± 0.4 (96) | 1.7 ± 0.7 (68) | 1.6 ± 0.5 (71) | >100 (0) |
| PnCS1[R3A] | 1.8 ± 0.3 (86) | 1.6 ± 0.5 (89) | >100 (51) | 1.9 ± 0.4 (87) | >100 (0) |
| PnCS1 [W4A] | 0.8 ± 0.3 (89) | 0.7 ± 0.3 (95) | 3.4 ± 0.2 (82) | 1.2 ± 0.3 (76) | >100 (0) |
| PnCS1[R6A] | 9.2 ± 1.1 (73) | 0.5 ± 0.2 (90) | 7.6 ± 2.2 (78) | 0.9 ± 0.2 (96) | >100 (0) |
| PnCS1 [W7A] | 0.8 ± 0.3 (92) | 1.1 ± 0.4 (96) | 6.8 ± 1.3 (78) | 11.4 ± 3.6 (57) | >100 (0) |
| PnCS1[N8A] | 0.9 ± 0.3 (96) | 0.9 ± 0.4 (94) | 2.2 ± 0.7 (92) | 0.8 ± 0.3 (89) | >100 (0) |
| PnCS1[R9A] | 6.7 ± 1.2 (80) | 1.1 ± 0.3 (86) | 9.2 ± 4.6 (72) | 0.9 ± 0.4 (79) | >100 (0) |
| PnCS1[R2K] | 1.1 ± 0.5 (92) | 0.8 ± 0.3 (93) | 2.5 ± 0.5 (82) | 0.6 ± 0.2 (85) | >100 (0) |
| PnCS1[R3K] | 0.8 ± 0.3 (96) | 0.6 ± 0.3 (92) | 2.7 ± 0.6 (94) | 0.8 ± 0.3 (86) | >100 (0) |
| PnCS1 [W4K] | 0.5 ± 0.4 (75) | 0.7 ± 0.4 (94) | 2.7 ± 0.5 (89) | 0.7 ± 0.4 (92) | >100 (0) |
| PnCS1[A5K] | 1.2 ± 0.4 (84) | 1.9 ± 0.8 (91) | 2.1 ± 0.2 (92) | 0.7 ± 0.3 (93) | >100 (0) |
| PnCS1[R6K] | 8.7 ± 2.4 (67) | 0.6 ± 0.4 (94) | 3.3 ± 1.5 (89) | 0.9 ± 0.3 (88) | >100 (0) |
| PnCS1 [W7K] | 2.8 ± 0.5 (71) | 1.7 ± 0.5 (87) | 3.0 ± 0.7 (90) | 8.2 ± 0.6 (82) | >100 (0) |
| PnCS1[N8K] | 4.4 ± 0.8 (81) | 0.9 ± 0.3 (96) | 2.8 ± 0.5 (86) | 0.5 ± 0.2 (92) | >100 (0) |
| PnCS1[R9K] | 10.2 ± 4.3 (62) | 6.1 ± 2.1 (66) | 9.2 ± 0.6 (67) | 6.7 ± 0.8 (72) | >100 (0) |
| PnCS1[R2E] | >100 (41) | >100 (11) | >100 (27) | >100 (5) | >100 (0) |
| PnCS1[R3E] | >100 (52) | >100 (36) | >100 (21) | >100 (24) | >100 (0) |
| PnCS1 [W4E] | 13.2 ± 5.2 (72) | 12.8 ± 4.1 (59) | >100 (34) | 14.8 ± 3.9 (67) | >100 (0) |
| PnCS1[A5E] | 1.4 ± 0.2 (81) | >100 (35) | 8.8 ± 3.7 (73) | 1.8 ± 0.5 (82) | >100 (0) |
| PnCS1[R6E] | >100 (49) | >100 (0) | >100 (19) | >100 (41) | >100 (0) |
| PnCS1 [W7E] | >100 (21) | >100 (42) | >100 (33) | >100 (27) | >100 (0) |
| PnCS1[N8E] | >100 (47) | >100 (53) | >100 (44) | >100 (27) | >100 (0) |
| PnCS1[R9E] | >100 (49) | >100 (0) | >100 (40) | >100 (11) | >100 (0) |
| PnCS1 [W4Y] | >100 (39) | >100 (33) | >100 (43) | >100 (42) | >100 (0) |
| PnCS1 [W7Y] | 7.4 ± 4.2 (76) | 7.8 ± 3.3 (73) | 11.7 ± 4.1 (75) | 0.7 ± 0.3 (93) | >100 (0) |
| PnCS1AcAm | >100 (0) | >100 (0) | >100 (0) | >100 (0) | >100 (0) |
| PnCS1DeAm | >100 (34) | >100 (43) | >100 (10) | >100 (24) | >100 (0) |
| PnCS1Ac | >100 (0) | >100 (0) | >100 (0) | >100 (0) | >100 (0) |
a
IC50 values in μM for n > 6, ± SD
b
Maximum % inhibition of peptides at 100 μM indicated in brackets with % inhibition ≥ 95 indicated in bold.