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Double-enzyme system probe and application thereof

An enzyme system and probe technology, applied in the field of nuclear medicine, can solve problems such as poor prognosis, resistance, tumor cell mutation, etc., and achieve the effect of broad application prospects

Active Publication Date: 2021-03-30
PEKING UNIV FIRST HOSPITAL
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  • Abstract
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  • Claims
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Problems solved by technology

Prostate cancer lesions can be treated with radiotherapy and surgery, and endocrine therapy for advanced prostate cancer can also achieve very good results, but castration resistant prostate cancer (CRPC) is not sensitive to endocrine therapy and radiotherapy , and the prognosis is very poor; nuclide-targeted therapy has shown an effective control rate of up to 80% in the targeted therapy for advanced castration-resistant prostate cancer, but the slow treatment cycle will lead to tumor cell mutations, which in turn produce resistance. sex

Method used

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  • Double-enzyme system probe and application thereof
  • Double-enzyme system probe and application thereof
  • Double-enzyme system probe and application thereof

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Embodiment Construction

[0063] Preferred embodiments of the present invention will be described in more detail below. Although preferred embodiments of the present invention are described below, it should be understood that the present invention can be embodied in various forms and should not be limited by the embodiments set forth herein.

[0064] Preparation of Probe A, Probe B, Probe C and Probe D

[0065] The specific structure of Probe A-D is as follows figure 2 shown. Synthetic steps such as image 3 shown. Coupling of amino acids was performed according to standard Fmoc solid phase synthesis.

[0066] image 3A general route for the preparation of Probes A-D is shown. Reaction conditions: (a) Fmoc-L-aspartic acid 4-tert-butyl ester, HATU and DIPEA in DCM; (b) TFA in DCM; (c) 2-chlorotriphenyl chloride resin and DIPEA in DMF / DCM solution; (d) DMF solution of 20% piperidine, DMF solution of Fmoc-L-valine, HBTU, HOBt and DIPEA; (e) DMF solution of 20% piperidine, N-Fmoc-L-glucose DMF ...

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Abstract

The invention belongs to the field of nuclear medicine, and relates to a double-enzyme system probe and application thereof. The probe has a structure shown as a formula I, and QD is a fluorophore ora drug group; L is a linker and has a structure as shown in a formula II; T is a PSMA specific targeting group; and Z is H, a nuclide chelating group, radionuclide or a nuclide chelating group chelated with radionuclide. The double-enzyme system nuclear medical probe for delivering drug molecules based on prostate specific membrane antigen PSMA targeting and Caspase-3 recognition strategies can target prostate cancer to perform radiotherapy sensitization treatment, is beneficial to solving the problems of radiotherapy resistance, targeted nuclide treatment resistance and the like of castration-resistant prostate cancer patients, and is expected to realize navigation in prostate cancer surgery. More efficient tools are provided for detection and treatment of tumor treatment, and wide application prospects are achieved.

Description

technical field [0001] The invention belongs to the field of nuclear medicine, and in particular relates to a dual-enzyme system probe and its application. Background technique [0002] Prostate cancer is the second most lethal malignancy among men, and ranks first in cancer incidence in Western developed countries. With the continuous development of my country's economy and society, the problem of population aging is prominent, the process of urbanization and industrialization is accelerating, and unhealthy lifestyles and chronic infection factors are gradually accumulating. The incidence and mortality of prostate cancer are increasing every year. Prostate cancer lesions can be treated with radiotherapy and surgery, and endocrine therapy for advanced prostate cancer can also achieve very good results, but castration resistant prostate cancer (CRPC) is not sensitive to endocrine therapy and radiotherapy , and the prognosis is very poor; nuclide-targeted therapy has shown an...

Claims

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Application Information

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IPC IPC(8): C07K7/02C07K1/13A61K51/08A61K49/00A61K47/64A61P35/00
CPCC07K7/02A61K51/08A61K49/0056A61K47/64A61P35/00
Inventor 杨兴刘昭飞徐红闯王琰璞张宁范岩杨志高献书
Owner PEKING UNIV FIRST HOSPITAL
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