The invention discloses a preparation method of a targeted
drug polypeptide for
glioma treatment, which comprises the following steps: 1) preparing a
small molecule inhibitor couple TGN020-5ca of AQP4, and the
structural formula of the TGN020-5ca is as follows: 2) sequentially adding different amino acids into a
solid-
phase synthesis tube to obtain a polypeptide, and reacting the polypeptide with
trimethylbromosilane and
methanol to obtain a methyl esterified polypeptide; and 3) preparing the polypeptide-TGN020: firstly adding N-hydroxysuccinimide and N, N '-diisopropyl
carbodiimide, activating carboxyl on the TGN020-5ca at the
activation temperature of 37-60 DEG C for 6-8 hours, then adding polypeptide or methyl esterified polypeptide and N, N-diisopropyl
ethylamine, and reacting at the temperature of 25-37 DEG C for 1-2 hours, the
molar ratio of the TGN020-5ca to the polypeptide or methyl esterified polypeptide being 1.2: 1-1.5: 1. The polypeptide TGN020 is targeted and accumulated on a
glioma cell membrane, can inhibit the rate of water molecules entering and exiting from
glioma cells in a long-acting manner, effectively inhibits the malignant
proliferation rate of glioma, has the capabilities of targeted enrichment and long-acting AQP4 inhibition, and has excellent
glioma cell killing capability.