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A kind of erythropoietin mimic peptide and its preparation method and application

An erythropoietin and peptidomimetic technology, applied in the field of erythropoietin peptidomimetic and its preparation and use, can solve the problems of low EC50 and limitation, and achieve the effect of prolonging half-life

Active Publication Date: 2019-01-08
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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  • A kind of erythropoietin mimic peptide and its preparation method and application
  • A kind of erythropoietin mimic peptide and its preparation method and application
  • A kind of erythropoietin mimic peptide and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Example 1 Synthesis of Erythropoietin Mimetic Peptide

[0057] The present invention will be described in further detail below in conjunction with specific examples.

[0058] The erythropoietin mimetic peptide of the present invention is an alkanoic acid conjugate, wherein the preparation of the peptide chain uses the Fmoc solid-phase peptide synthesis method, and the CS 336X instrument produced by CSBio Company is used to synthesize the peptide 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....

Embodiment 2

[0069] Example 2. Effect of erythropoietin mimetic peptide on mice

[0070] Using mice to evaluate and compare the effects of erythropoietin mimetic peptide and erythropoietin protein on mouse erythropoiesis.

[0071] Among them, EPO (recombinant human erythropoietin injection, approval number: Guoyao Zhunzi S20000026) was purchased from Shenyang Sansheng Pharmaceutical Co., Ltd.;

[0072] 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 4 groups.

[0073] Among them, two groups of mice were subcutaneously injected with erythropoietin mimetic peptide 1 and 2 respectively; a group of mice were injected with erythropoietin protein; 4.5 mg / kg for three consecutive days, then sacrifice the mice, take whole blood for counting peripheral blood cells and reticulocytes, and count the blood cells with an automatic blood cell cou...

Embodiment 3

[0077] Example 3: Effects of Erythropoietin Mimetic Peptides on Rhesus Monkeys

[0078] Rhesus monkeys were used to evaluate the effect of erythropoietin-mimetic peptides on erythropoiesis. Rhesus monkeys, weighing 5.5-8.5 kg, male or female, were purchased from Hainan Experimental Animal Center. The macaques were divided into four groups according to the basic hemoglobin, with three animals in each group. The control group was injected with PBS buffer (25Mm / l), one group was treated with mimetic peptide 1, and the other group was treated with mimetic peptide 2, intravenously injected once a week, 4.5mg / kg each time, and a group was treated with EPO, three times / week, each time 240μ / kg, continuous administration for three weeks, and hematological indicators were measured once a week. The experimental results are shown in Table 2:

[0079] Table 2. Effects of erythropoietin mimetic peptides on rhesus monkey reticulocyte production

[0080]

[0081]

[0082] It was fo...

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Abstract

The invention relates to a hmopoietin mimic peptide with long-acting erythropoiesis-promoting function and pharmaceutical salts. The invention also provides a preparation method for the above mopoietin mimic peptide and application of the mopoietin mimic peptide to prepare medicines treating diseases with the character of erythrocyte lack, erythropoietin lack, or erythrocyte population lack or defect. The provided hemopoietin mimic peptide is an alkyl acid conjugate of a lysine (K) side-chain dissociated amino at the terminal of a peptide chain shown as SEQ ID NO:1, the structural general formula is shown as a formula I: GGLYACHMGPITNalVCQPLRSarK-X, wherein two cysteine form a disulfide bond, the N terminal is acylated, and X represents lauric acid or palmitic acid.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to an erythropoietin mimic peptide. An agonistic erythropoietin mimetic peptide and a preparation method thereof. The present invention also 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 deficiency 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 β-type contains 26% carbohydrates. The two types are identical in biological characteristics, antigenicity and ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/00C07K1/16C07K1/06C07K1/04A61K38/16A61P13/12A61P7/06A61P37/02A61P35/00A61P25/00A61P29/00
CPCA61K38/00C07K14/00
Inventor 龚珉魏群超夏广萍周植星赵娜夏郑学敏韩英梅孔维苓王士伟
Owner TIANJIN INSTITUTE OF PHARMA RESEARCH
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