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C-terminal amino acid lactone modified extrasin alpha-1 and its uses

A technology of tryptophan lactone and amino acid, applied in application, gene therapy, genetic engineering, etc., can solve the problems of small molecule of thymosin α1, inability to obtain natural single-molecule expression product, and high cost of use, and achieve the goal of protecting hematopoietic function Effect

Inactive Publication Date: 2007-09-05
西安迪赛生物药业有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In addition, due to the small molecule of thymosin α1, natural single-molecule expression products cannot be obtained in prokaryotic expression systems such as Escherichia coli
At present, thymosin α1 is mainly prepared by chemical synthesis, but the problem is that the cost of use is too high

Method used

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  • C-terminal amino acid lactone modified extrasin alpha-1 and its uses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1 Thymosin α1 polypeptide modified by methionine derivatives at the C-terminus

[0022] The sequence of the thymosin α1 polypeptide whose C-terminus is modified by a methionine derivative is as follows:

[0023] SerAspAlaAlaValAspThrSerSerGluIleThrThrLysAspLeuLysGluLysLysGluValValGluGluAlaGluAsn-homoserine lactone

[0024] 1. Preparation method

[0025] The thymosin α1 polypeptide whose C-terminus is modified with homoserine lactone can be produced by using techniques known in the art.

[0026] 1) Peptide chemical synthesis combined with chemical modification

[0027](1) Polypeptide solid-phase synthesis is a mature technology. As long as the amino acid sequence is given, many companies can carry out large-scale synthesis according to the given amino acid sequence. According to the Fmoc solid-phase synthesis method (Fmoc: 9-fluorenylmethoxycarbonyl), on Applied Biosystems company's 433 type peptide synthesizer, the chemically synthesized amino acids are as fo...

Embodiment 2

[0096] Example 2 Thymosin α1 polypeptide modified by tryptophan derivatives at the C-terminus

[0097] 1. Preparation method

[0098] The thymosin α1 polypeptide whose C-terminus is modified by tryptophan lactone can be produced by techniques known in the art.

[0099] 1) Peptide chemical synthesis combined with chemical modification

[0100] Same as Example 1, the difference is that the last amino acid in the synthetic amino acid sequence is not methionine but tryptophan. The amino acid sequence is as follows:

[0101] SerAspAlaAlaValAspThrSerSerGluIleThrThrLysAspLeuLysGluLysLysGluValValGluGluAlaGluAsnTrp

[0102] The above synthetic product was modified with N-chlorosuccinimide to tryptophan according to the experimental method of the aforementioned "Chemical reagents for protein modification". The synthetic product was dissolved in 50% acetic acid at 2 mg / ml (in a pressure-resistant container that can be sealed), and then N-chlorosuccinimide was added to a final concent...

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Abstract

The present invention relates to polypeptide thymosin alpha-1 derivative, and is especially C-terminal amino acid lactone modified thymosin alpha-1. The C-terminal amino acid lactone modified thymosin alpha-1 of the present invention has bioactivity higher than that of natural thymosin alpha-1, and new bioactivity not possessed by natural thymosin alpha-1. For example, the C-terminal amino acid lactone modified thymosin alpha-1 can resist the hematogenesis function inhibition caused by chemotherapeutic medicine and radiotherapy, so that it is suitable for use in the auxiliary treatment of chemotherapy and radiotherapy of viral diseases and tumors. The present invention also relates to coding nucleic acid of the thymosin alpha-1 derivative, medicine composition containing the thymosin alpha-1 derivative and their use.

Description

technical field [0001] The invention relates to biological polypeptide thymosin α1 derivatives. More specifically, the present invention relates to thymosin α1 whose C-terminus is modified with an amino acid lactone. The thymosin α1 derivatives described in the present invention not only have stronger biological activity than the known biological activity of natural thymosin α1, but also have new biological activities that natural thymosin α1 does not possess, such as anti-chemotherapy drugs or Inhibition of hematopoietic function caused by radiotherapy, so it is more suitable for adjuvant treatment of antiviral therapy, antitumor therapy, chemotherapy and radiotherapy. The present invention also relates to the encoding nucleic acid of the thymosin α1 derivative, the pharmaceutical composition containing the thymosin α1 derivative and the use thereof. Background technique [0002] Thymosin-α1 (Thymosinα1) was first discovered in thymus tissue by Goldstein et al. in 1977. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/435C12N15/12C12N15/63A61K48/00A61P1/16A61P31/14A61P31/18A61P31/16A61P35/00A61P1/12A61P31/00
Inventor 吴建中
Owner 西安迪赛生物药业有限责任公司
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