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

An erythropoietin and peptidomimetic technology, applied in the field of erythropoietin peptidomimetic and its preparation and application, can solve problems such as 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 mimetic peptide and its preparation method and application
  • A kind of erythropoietin mimetic peptide and its preparation method and application
  • A kind of erythropoietin mimetic peptide and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Synthesis of Erythropoietin Mimetic Peptide

[0039] The present invention will be described in further detail below in conjunction with specific examples.

[0040] The erythropoietin mimetic peptide of the present invention is a polypeptide, which can be prepared using the Fmoc solid-phase polypeptide synthesis method, and the CS 336X instrument produced by CSBio Company 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. The synthesized polypeptide was di...

Embodiment 2

[0041] Example 2 Effects of erythropoietin mimetic peptide on mice

[0042] Using mice to evaluate and compare the effects of erythropoietin mimetic peptide and erythropoietin protein on mouse erythropoiesis.

[0043] Among them, EPO drugs were purchased from Shenyang Sansheng Pharmaceutical Co., Ltd.;

[0044] Kunming mice, purchased from Shanghai Experimental Animal Center of 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.

[0045] Among them, the mice in the experimental group were injected with erythropoietin mimic peptide, the mice in the positive control group were injected with erythropoietin protein, and the mice in the negative control group were blank controls and injected with PBS buffer at a dose of 4.5 mg / kg. Three days later, the mice were sacrificed, and the whole blood was taken to count peripheral blood cells and reticulocytes, and the blood cell counts wer...

Embodiment 3

[0049] Example 3 Effects of erythropoietin mimetic peptide on macaques

[0050] 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 two groups according to the basic hemoglobin, with three monkeys in each group. The experimental group used the erythropoietin mimetic peptide of the present invention, intravenously injected once a week, each 4.5mg / kg, and the control group used EPO, three times / week, each 240 μ / kg, administered continuously for five weeks, measured every week 1 blood test

[0051] The results are shown in Table 3. A single intravenous injection of erythropoietin-mimetic peptides led to an increase in the hemoglobin content (33%) and hematocrit in the peripheral blood of rhesus monkeys, indicating that the derivatives stimulate hemoglobin production. The positive control er...

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Abstract

The invention relates to erythropoietin mimic peptide and a medicinal salt thereof. The invention further provides application of the erythropoietin mimic peptide in drug used for treating diseases featured by erythrocyte deficiency or erythrogenin deficiency or erythrocyte group deficiency or defect. Amino acid sequence of the erythropoietin mimic peptide is shown as SEQ ID NO:1 GGLYAX1GHMGPIX2VX3GQPLRX4K, wherein X1 and X3 are allylglycine, X2 is 3-(1-naphthyl)-L-alanine, X3 is sarcosine, olefinic bonds are formed between allylglycine through olefin metathesis, and N terminal is acetylized. The erythropoietin mimic peptide can promote generation of erythrocytes, and half-life period of the drug in vivo is prolonged remarkably.

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): C07K14/505C07K1/20C07K1/04A61K38/18A61P13/12A61P7/08A61P7/06A61P37/02A61P35/00A61P29/00A61P39/06
CPCA61K38/00C07K14/505
Inventor 龚珉夏广萍王士伟郑学敏赵娜夏魏群超韩英梅周植星
Owner TIANJIN INSTITUTE OF PHARMA RESEARCH
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