A kind of prodrug activation compound, prodrug system and its preparation method and application

Abstract

The present invention provides a prodrug activating compound, characterized in that the prodrug activating compound comprises a polypeptide fragment, and a tetrazine group and a hydrophobic group connected to the polypeptide fragment by chemical bonds; the amino acid of the polypeptide fragment has at least one phosphorylated tyrosine. The prodrug activating compound provided by the present invention has targeting and specificity, can quickly and efficiently accumulate in tumor cells and self-assemble in situ to form a nano-assembly, and then efficiently and specifically activate trans-cyclooctene-modified Antitumor prodrug; the prodrug activating compound and the prodrug system of the present invention have good biocompatibility and no systemic toxicity. The preparation method of the prodrug activating compound adopts a solid-phase synthesis method, the operation is simple, and the obtained product has high chemical purity and high total yield.

Description

technical field [0001] The invention belongs to the technical field of chemistry and medicine, and in particular relates to a prodrug activating compound, a prodrug system and a preparation method and application thereof. Background technique [0002] In tumor treatment, the use of small molecule chemotherapeutic drugs is often accompanied by serious drug side effects (Adverse Drug Reactions, ADR), because small molecule drugs lack selective recognition of tumor cells, and often have negative effects on normal tissues around the tumor and even other organs. Cause toxic side effects, greatly limit the dosage, which may lead to the failure of chemotherapy. Prodrugs (prodrugs, pro-drugs) are currently an important method to alleviate the side effects of chemotherapy drugs. After a designated area in the body is activated by the microenvironmental difference (such as overexpressed enzymes, oxidants, or reductants, etc.) or exogenous stimuli (such as light, magnetism, or ultraso...

AI Technical Summary

Problems solved by technology

[0004] However, in the prior art, traditional tumor targeting mainly includes active targeting tumor strategies relying on antibody proteins and passive targeted delivery strategies relying on nanocarriers. Although the active targeting of antibody proteins has good targeting, it is still Faced with difficulties such as low drug loading efficiency of antibodies, differences in tumor antigen expression, and difficulty in antibody endocytosis, resulting in low drug targeting efficiency; passive targeting relying on nanocarriers faces the problem of low delivery efficiency

Moreover, the currently developed prodrugs all realize the release and activation of the parent drug under the conditions of endogenous activation or exogenous stimuli, and endogenous activation conditions such as overexpression of enzymes, oxides, and reductants also exist in normal cells. However, exogenous stimuli such as light, magnetic field, and ultrasound are not only complicated and expensive to operate, but also inevitably cause damage to normal tissues.

Images