| 摘要 |
Provided in the present invention are a YAP protein inhibiting polypeptide and application thereof. In particular, the present invention obtains a key binding site of YAP protein and TEAD, screens a polypeptide with best YAP inhibitory activity and modifies the polypeptide, such as adding a disulfide linkage, replacing an amino acid, removing and/or adding (for example, adding a cell-penetrating element), and finally screens and verifies the obtaining of a series of polypeptides with YAP protein activity inhibiting effect and good stability. Experiments show that the polypeptide of the present invention can effectively inhibit the binding activity between YAP protein and TEAD, thus providing good therapeutic effect on digestive tract tumors (especially liver cancer). |
| 主权项 |
1. An isolated polypeptide, wherein the polypeptide has a structure as shown in formula A:
X0-Yi-Y2-Y3-Y4-Y5-Y6-XA-XE (A) wherein, X0 or XA is not present, or is 1, 2, 3, or 4 amino acid residues; Y1 is AP, VP, or not present; Y2 is X1-X2-X2a, wherein X1 is selected from M, F, C or Hcy; X2 is an arbitrary amino acid residue (preferably X2 is C, Hcy, L, M, or F); and X2a is L, Nle, C, Hcy, K or R; Y3 is X3a-X3-X4, wherein X3a is alkaline amino acid R or K; X3 is an arbitrary amino acid (preferably X3 is K, R, Hcy, C, Orn or Dab); and X4 is an arbitrary amino acid (preferably X4 is L, Nle, Hcy, or C), and at least one amino acid of Y3 is Hcy or C; Y4 is P; Y5 is X5, and X5 is an arbitrary amino acid (preferably X5 is A, D, or E); Y6 is S-X6a-X6, wherein X6a is F, C, or Hcy; and X6 is an arbitrary amino acid residue (preferably X6 is C, Hcy, F, K or R); Y7 is X7-P-X7a, wherein X7 is an arbitrary amino acid residue (preferably X7 is C, Hcy, K, R or P); X7a is C, Hcy or P; XE is not present or is a cell-penetrating element; and the polypeptide exhibits an inhibitory activity on Yes-associated protein (YAP). |
