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Intelligent anticoagulant nucleic acid aptamer with pH response, application of intelligent anticoagulant nucleic acid aptamer and medicine

A nucleic acid aptamer and anticoagulant technology, which is applied in drug combinations, antineoplastic drugs, and medical preparations containing active ingredients, etc., can solve problems such as intelligent thrombin aptamers that have not yet been reported, and achieve high Anticoagulant effect, prevention of thrombosis, high affinity effect

Active Publication Date: 2022-04-15
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] Although studies on thrombin aptamers such as HD1, HD22, and HD1-HD22 have been published, there have been no reports on intelligent thrombin aptamers

Method used

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  • Intelligent anticoagulant nucleic acid aptamer with pH response, application of intelligent anticoagulant nucleic acid aptamer and medicine
  • Intelligent anticoagulant nucleic acid aptamer with pH response, application of intelligent anticoagulant nucleic acid aptamer and medicine
  • Intelligent anticoagulant nucleic acid aptamer with pH response, application of intelligent anticoagulant nucleic acid aptamer and medicine

Examples

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Embodiment 1

[0042] This example relates to the screening process of pH-responsive smart anticoagulant nucleic acid aptamers.

[0043] The design idea of ​​the present invention is based on the fact that some nucleic acid sequences rich in C bases can be folded and shortened under acidic conditions, by changing the bridge arms between the bivalent aptamers to nucleic acid sequences rich in C Purpose of pH response. Based on this, the present invention introduces a pH-responsive sequence into the bivalent aptamer by modifying the spacer of the HD1-HD22 bivalent aptamer, and produces an acidic pH ~ 5 lowering aptamer that can be used in cancer and other lesions. Its anticoagulant effect can avoid hemorrhage at the cancer site; normal anticoagulation in normal parts, etc., reflects the specific effect of anticoagulation to prevent thrombus. However, since the sequences of HD1 and HD22 contain a large number of G bases, it is very easy to form base complementarity with the C bases in the acid...

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Abstract

The invention relates to a pH-responsive intelligent anticoagulant nucleic acid aptamer, the anticoagulant nucleic acid aptamer is an HD1-HD22 bivalent aptamer, an HD1 aptamer or a derivative thereof is connected with an HD22 aptamer or a derivative thereof through a bridge arm, and the bridge arm is a sequence with a pH-responsive characteristic; the sequence of the bridge arm is 5 '-TTCCTATCCGTTCCGATCCG-3' or 5 '-TTCCTATCCGTTCCAATCCG-3', and the sequence of the bridge arm is 5 '-TTCCTATCCGTTCCAATCCG-3'; the bridge arm is rich in a nucleic acid sequence of a C basic group, has the characteristic of folding and shortening the length under an acidic condition, and does not form basic group complementation with G basic groups in HD1 and HD22 sequences or destroy the structure and function of a single-chain aptamer, and the thrombin aptamers HD1 and HD22 of the bridge arm are connected to obtain the pH-responsive intelligent anticoagulant bivalent aptamer. The bivalent aptamer not only has the excellent characteristics of a common bivalent aptamer, but also can solve the problem of massive hemorrhage caused by the fact that a cancer focus compresses a weak part of a blood vessel or continuous hemorrhage of the part where the cancer focus compresses the blood vessel due to thrombocytopenia while anti-cancer thrombus treatment is carried out.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a pH-responsive intelligent anticoagulant nucleic acid aptamer and its application and medicine. Background technique [0002] Tumor thrombus is one of the common complications of tumors. In recent years, studies have found that abnormal blood coagulation is common in malignant tumor patients, and hypercoagulable state is prone to concurrent thrombosis, which is the second cause of death after malignant tumor itself. Cancer embolus refers to cancer cells invading or accumulating blood vessels and lymphatic system during the process of growth, reproduction, and metastasis, or causing abnormal blood coagulation, resulting in vascular function and blood circulation disorders, abnormal coagulation, and thrombus formation, resulting in a series of pathophysiological changes tumor complications. More than 90% of malignant tumor patients may have abnormal blood coagulation system ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/115A61K31/713A61P7/02A61P35/00
CPCY02A50/30
Inventor 刘建宇高庆杰张文科
Owner JILIN UNIV
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