| 主权项 |
1. An isolated non-natural Huwentoxin-IV variant comprising the sequence X1CX2X3X4FX5X6CX7X8X9X10X11X12CCX13X14 X15X16X17X18CX19X20X21X22X23 X24CKX25X26IX27X28 (SEQ ID NO: 357); wherein
i) X1 is K, R, H, D, Y, F, N, Q, S, T, G, L, I, P or E; ii) X2 is R, F, W, N, S or L; iii) X3 is R, H, D, Y, N, Q, L, I, P or E; iv) X4 is Y, V or I; v) X5 is R, W, Q, S or K; vi) X6 is R, E, Y, F, V or A; vii) X7 is K, R, E, Y, F, S, V or N; viii) X8 is P or V; ix) X9 is R, F, Q, V or S; x) X10 is H, D, Y, W, Q, S, T, G, A, V, L, I, P or N; xi) X11 is D, P or W; xii) X12 is K, R, D, E, Y, W, N, T, A, L or Q; xiii) X13 is R, Y, Q, S, T, G, L, I, P or K; xiv) X14 is K, R, Y, F, N, Q, G, A, V, L, I, P or S; xv) X15 is R, H, D, Y, W, N, Q, T, V, I, P or S; xvi) X16 is R, H, D, F, W, N, Q, S, T, G, A, L or K; xvii) X17 is K, R, Y, F, W, P or L; xviii) X18 is K, R, T, A, L or V; xix) X19 is S or I; xx) X20 is K, W, G, A, I, R or D; xxi) X21 is Y, W, A, H or K; xxii) X22 is T or V; xxiii) X23 is K, H, W, N, G, A, L or R; xxiv) X24 is W or K; xxv) X25 is W, T, I or Y; xxvi) X26 is K, R, Y, F, S, T, G, A, V, L, I or Q; xxvii) X27 is K, R, H, F, W, V, L, I, G or deleted; and xxviii) X28 is R, H, Y, F, W, N, G, V, P, K or deleted, and
the non-natural Huwentoxin-IV variant has an IC50 value of about 300×10−9 M or less for human Nav1.7 (SEQ ID NO: 263), with the proviso that the non-natural Huwentoxin-IV variant is not a polypeptide comprising the sequence shown in SEQ ID NO: 1. |
