Prodrug activation compound, prodrug system, preparation method and application thereof

Abstract

The invention provides a prodrug activation compound, which is characterized by comprising a polypeptide fragment, and a tetrazine group and a hydrophobic group which are connected to the polypeptidefragment through chemical bonds; wherein at least one phosphorylated tyrosine exists in the amino acid of the polypeptide fragment. The prodrug activation compound provided by the invention has targeting property and specificity, can be quickly and efficiently accumulated in tumor cells and is self-assembled in situ to form a nano assembly, so that a trans-cyclooctene modified anti-tumor prodrug is efficiently and specifically activated; the prodrug activating compound and the prodrug system are good in biocompatibility and free of system toxicity. A solid-phase synthesis method is adopted inthe preparation method of the prodrug activated compound, the operation is simple, and the obtained product is high in chemical purity and high in 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.

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