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Long-acting erythropoietin mimic peptide, and preparation method and application thereof

An erythropoietin and peptide-mimicking technology, applied in the field of biomedicine, can solve the problems of low EC50 and limitation, and achieve the effect of prolonging the half-life

Active Publication Date: 2017-04-05
TIANJIN INSTITUTE OF PHARMA RESEARCH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the EC50 of peptides that can stimulate erythrocyte proliferation and differentiation is very low, between 20nM and 250nM, so the clinical application of these peptides is greatly limited

Method used

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  • Long-acting erythropoietin mimic peptide, and preparation method and application thereof
  • Long-acting erythropoietin mimic peptide, and preparation method and application thereof
  • Long-acting erythropoietin mimic peptide, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1 Synthesis of Erythropoietin Mimetic Peptide

[0053] The present invention will be described in further detail below in conjunction with specific examples.

[0054] The erythropoietin mimetic peptide of the present invention is a polypeptide whose sequence is selected from SEQ ID NO:1. Using the Fmoc solid-phase polypeptide synthesis method, the CS 336X instrument produced by CSBio Company was used to synthesize the polypeptide of the present invention. The method of synthesis was carried out according to the manufacturer's instruction manual. The Fmoc solid-phase polypeptide synthesis method described herein refers to a synthetic method in which a polymer resin is used as a solid-phase reaction matrix to sequentially condense amino-terminal Fmoc-protected amino acids in the presence of a coupling reagent to synthesize a polypeptide. For its specific method, see Fmoc solid phase peptide synthesis: a practical approach, 2000, Oxford University Press. And t...

Embodiment 2

[0056] Example 2. Effect of erythropoietin mimetic peptide on mice

[0057] Using mice to evaluate and compare the effects of erythropoietin mimetic peptide and erythropoietin protein on mouse erythropoiesis.

[0058] Among them, EPO (recombinant human erythropoietin injection, batch number: 201405YC12) was purchased from Shenyang Sansheng Pharmaceutical Co., Ltd.;

[0059] Kunming mice, purchased from Shanghai Experimental Animal Center, Chinese Academy of Sciences, weighing 25-30 g, are all female mice. The number of animals in each group in the experiment: 10, divided into 3 groups.

[0060] Wherein, a group of mice were injected with the erythropoietin mimic peptide derivative synthesized in Example 1, a group of mice were injected with erythropoietin protein, a group of mice were blank controls, and injected with PBS buffer (25mM / l) , the dose was 4.5mg / kg, for three consecutive days, and then the mice were sacrificed, and the whole blood was taken for peripheral blood...

Embodiment 3

[0064] Example 3: Effects of Erythropoietin Mimetic Peptides on Rhesus Monkeys

[0065] Rhesus monkeys were used to evaluate the effect of erythropoietin-mimetic peptides on erythropoiesis. Rhesus monkeys, weighing 5.5-.5 kg, male or female, were purchased from Hainan Experimental Animal Center. The macaques were divided into two groups according to the basic hemoglobin, with three monkeys in each group. One group used the mimic peptide synthesized in Example 1, intravenously injected once a week, 4.5mg / kg each time; one group used EPO, three times / week, each time 240μ / kg, administered continuously for five weeks, and measured once a week Hematological indicators, as shown in Table 2.

[0066] Table 2: Effects of erythropoietin mimetic peptide derivatives on rhesus monkey reticulocyte production

[0067] name dose reticulocyte count blank PBS buffer 223.12±1.26 SEQ ID NO:1 4.5mg / kg 729.34±2.10 EPO 4.5mg / kg 536.28±1.86

[0068] It ...

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Abstract

The invention relates to an erythropoietin mimetic peptide derivative having a long-acting erythropoiesis function and a medicinal salt thereof. The invention also provides a preparation method of the erythropoietin mimetic peptide derivative, and a use of the erythropoietin mimetic peptide derivative in the preparation of medicines for treating diseases characterized by lacking of erythropoietin or erythrocyte population deficiency or defect. The erythropoietin mimetic peptide derivative is a polypeptide represented by SEQ ID NO:1 GGLYACHMGPITNalVCQPLRSarKVPGPGVPGPGVPGPGVPGPG, wherein two cysteines of the polypeptide form a disulfide bond, and the N end is acetylated.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to an erythropoietin mimic peptide. Specifically, the present invention relates to an erythropoietin mimetic peptide capable of binding to and activating erythropoietin receptors, or capable of agonizing erythropoietin, and a preparation method thereof. It relates to the use of the mimetic peptide in the preparation of medicines for treating diseases characterized by the lack of erythropoietin or the absence or defect of red blood cell populations. Background technique [0002] Erythropoietin (EPO) is a glycoprotein hormone with a molecular weight of about 34kD. The erythropoietin present in the plasma is composed of 165 amino acids, with a high degree of glycosylation, and the main sugar component is sialic acid. According to different carbohydrate content, naturally occurring erythropoietin is divided into two types, α-type and β-type, among which, α-type contains 34% carbohydrates, and ...

Claims

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Application Information

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IPC IPC(8): C07K14/00A61K38/16A61P13/12A61P7/06A61P37/02A61P35/00A61P25/00A61P29/00
CPCA61K38/00C07K14/00
Inventor 龚珉郑学敏魏群超韩英梅赵娜夏夏广萍周植星孔维苓王士伟
Owner TIANJIN INSTITUTE OF PHARMA RESEARCH
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