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Antitumor polypeptide and application thereof

An anti-tumor and anti-tumor drug technology, applied in the field of anti-tumor drug research and development and application, can solve the problem of low anti-cancer activity of 14 peptides, and achieve the effect of easy manufacture and significant anti-cancer effect.

Inactive Publication Date: 2013-03-27
何明忠
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Problems in the prior art: (1) the problems of the above-mentioned existing substances PX-478, polyamide, YC-1, TX-1845, TX-1846 and RNA antagonist EZN-2968 are unnatural synthetic drugs; (2) ) 14 peptides disclosed in Chinese patent ZL200510116615.1 have very low anticancer activity

Method used

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  • Antitumor polypeptide and application thereof
  • Antitumor polypeptide and application thereof
  • Antitumor polypeptide and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] The first polypeptide provided by the present invention is shown in SEQ ID NO: 1, which consists of 85 amino acids. 对应人类低氧诱导因子-1a第17位Arg至第101位Glu(85肽),ArgArgLysGluLysSerArgAspAlaAlaArgSerArgArgSerLysGluSerGluValPheTyrGluLeuAlaHisGlnLeuProLeuProHisAsnValSerSerHisLeuAspLysAlaSerValMetArgLeuThrIleSerTyrLeuArgValArgLysLeuLeuAspAlaGlyAspLeuAsp IleGluAspAspMetLysAlaGlnMetAsnCysPheTyrLeuLysAlaLeuAspGlyPheValMet,或者R R K E K S R D A A R S R R S K E S E V F Y E L A H QL P L P H N V S S H L D K A S V M R L T I S Y L R V RK L L D A G D L D I E D D M K A Q M N C F Y L K A L DG F V M(SEQ ID NO:1)

[0045] The polypeptide further provided by the present invention is a polypeptide consisting of at least 15 amino acids formed by consecutively reducing one or more amino acids from the C-terminus of the amino acid sequence shown in SEQ ID NO:1. For example:

[0046] 15 peptides: corresponding to the 17th Arg to ...

Embodiment 2

[0073] Usually, in order to reduce the production cost of the polypeptide, try to choose to produce a relatively short polypeptide on the premise of maintaining a relatively strong biological activity. Based on the above results, it was found that the 65 peptide was more effective in inhibiting tumor cell growth than the 45 peptide.

[0074] The difference between the 65 peptide and the 45 peptide is that the C-terminus of the 65 peptide has more sequence LeuThrIleSerLeuArgValArgLysLeuLeuAlaGlyAspLeuAspIleGlu than that of the 45 peptide. The length of this sequence is 20 amino acids, and it is this sequence that greatly increases the anti-tumor effect.

[0075] In order to identify the shortest effective length from the above 20 amino acid sequences, the following peptides were synthesized with the above 45 peptide (SEQ ID NO: 5) as the basic structure, adding 1-20 amino acids of varying numbers at the C-terminus:

[0076] 46 peptides:

[0077] ArgArgLysGluLysSerArgAspAlaAlaA...

Embodiment 3

[0121] In order to enhance the anti-tumor activity of the polypeptide, taking the 65 peptide with the strongest anti-tumor effect as an example, the following polypeptides were re-synthesized. They are based on 65 peptides and add sequences at the N-terminus and C-terminus respectively.

[0122] LysLysLysIl eSerSerGlu-65 Peptide:

[0123] LysLysLysI leSerSerGlu-ArgArgLysGluLysSerArgAspAlaAlaArgSerArgArgSerLysGluSerGluValPheTyrGluLeuAlaHisGlnLeuProLeuProHisAsnValSerSerHisLeuAspLysAlaSerValMetArgLeuThrI leSerTyrLeuArgValArgLysLeuLeuAspAlaGlyAspLeuAspIleGlu,或者K K K I S S E-R R K E K S R D A A R S R R S K E S E VF Y E L A H Q L P L P H N V S S H L D K A S V M R L TI S Y L R V R K L L D A G D L D I E(SEQ ID NO:27)

[0124] Corresponding to the 10th Lys to 16th Glu+65 peptide (17th Arg to 81st Glu) of human hypoxia inducible factor-1a protein.

[0125] 65 Peptide-GlnArgLysArgLysMet:

[0126]ArgArgLysGluLysSerArgAspAlaAlaArgSe...

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Abstract

The invention relates to antitumor polypeptide and application thereof. A cellular hypoxia reaction can induce expression of hypoxia-inducible factor-1alpha and initiate malignant tumors. According to identification of a hypoxia-inducible factor-1alpha protein sequence, a series of segments exist in an interval from the 10th position Lys to the 101st position Glu and an interval from the 717th position Gln to the 722nd position Met, but the segments or the polypeptide can inhibit growth and survival of cancer cells.

Description

technical field [0001] The invention relates to the field of research and development and application of anti-tumor drugs, in particular to various anti-tumor polypeptides and uses thereof. technical background [0002] Solid tumors are a hypoxic environment, and such an environment makes tumor treatment more difficult (Hoeckel M et al., Vaupel P. Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Research, 1996; 56: 4509-15.), this is because the response of tumor cells to the hypoxic environment plays an important role in the deterioration and evolution of tumors, and the results are manifested in tumor cell immortalization, genome instability, tumor angiogenesis, tumor cell Energy metabolism, tumor autocrine growth factor signal transduction, tumor invasion and metastasis (Hong SS et al. HIF-1alpha: a valid therapeutic target for tumor therapy. Cancer Research and Treatment. 2004Dec; 36(6): 343-53 .), but also red...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/435A61K38/17A61P35/02
Inventor 鲍丽娟何明忠
Owner 何明忠
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