Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Aliphatic-dicarboxylic-acid-coupled EPO mimic peptide derivative and preparation method and application thereof

A technology of aliphatic dicarboxylic acid and mimetic peptide, which is applied in the field of EPO mimetic peptide derivatives coupled with aliphatic dicarboxylic acid and its preparation and application, which can solve the problems of low EC50 and limitation, and achieve the effect of prolonging the half-life

Active Publication Date: 2017-05-03
天津天诚新药评价有限公司
View PDF5 Cites 0 Cited by
  • 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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Aliphatic-dicarboxylic-acid-coupled EPO mimic peptide derivative and preparation method and application thereof
  • Aliphatic-dicarboxylic-acid-coupled EPO mimic peptide derivative and preparation method and application thereof
  • Aliphatic-dicarboxylic-acid-coupled EPO mimic peptide derivative and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 Synthesis of Erythropoietin Mimetic Peptide Derivatives Coupled with Aliphatic Dicarboxylic Acid

[0049] 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. Select amino acids according to SEQ ID NO: 1, and synthesize a polypeptide whose sequence is shown in SEQ ID NO: 1 by Fmoc solid-phase peptide synthesis method, X 1 and x 3 Condensation of side-chain amino group...

Embodiment 2

[0050] Example 2 Effects of Erythropoietin Mimetic Peptide Derivatives Coupled with Aliphatic Dicarboxylic Acid on Mice

[0051] Using mice to evaluate and compare the effects of erythropoietin mimetic peptide derivatives and erythropoietin protein on mouse erythropoiesis.

[0052] Among them, EPO drugs were purchased from Shenyang Sansheng Pharmaceutical Co., Ltd.;

[0053] 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 4 groups.

[0054] Among them, the mice in group 1 were injected with erythropoietin mimetic peptide derivatives at a dose of 4.5 mg / kg, the mice in group 1 were injected with erythropoietin protein at a dose of 4.5 mg / kg, and the mice in group 1 were blank controls. After injecting PBS buffer solution for seven consecutive days, the mice were sacrificed, and the whole blood was collected for counti...

Embodiment 3

[0058] Example 3: Effects of Erythropoietin Mimetic Peptide Derivatives Coupled with Aliphatic Dicarboxylic Acid on Rhesus Monkeys

[0059] The EPO drug used in the present invention was purchased from Shenyang Sansheng Pharmaceutical Co., Ltd.

[0060] Rhesus monkeys were used to evaluate the effect of erythropoietin-mimetic peptide derivatives 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. One group used the mimetic peptide derivative dimer of the present invention, intravenously injected once a week, 4.5mg / kg each time; the other group used EPO as the positive control group, three times / week, 1.5mg / kg each time, continuously administered The medicine was given for five weeks, and the hematological indicators were measured once a week.

[0061] It was found that a single intravenous ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to an aliphatic-dicarboxylic-acid-coupled erythropoietin (EPO) mimic peptide derivative, which is monomer peptide having the sequence shown as SEQ ID NO: 1, GGLYAC6HMGPITX<1>VC15QPLRX<2>K, wherein X<2> is 3-(1-naphthyl)-L-alanine (Na1), X<4> is sarcosine (Sar), X<1> is K or R, X<3> is K or R, amino groups located at the side chains of X<1> and X<3> are connected into rings through linear aliphatic dicarboxylic acid such as propane diacid, maleic acid, succinic acid and glutaric acid, and an N terminal is acetylated. The invention further provides a preparation method of the mimic peptide derivative and pharmaceutically-acceptable salt of the mimic peptide derivative. The invention further provides a pharmaceutical composition containing the mimic peptide derivative or pharmaceutically-acceptable salt of the mimic peptide derivative. The EPO mimic peptide derivative and pharmaceutically-acceptable salt thereof can stimulate erythropoiesis and allows the half life of the medicine in the body to be obviously prolonged.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to an erythropoietin mimic peptide derivative. Erythropoietin mimetic peptide derivatives coupled with aliphatic dicarboxylic acid with agonistic effect of protopoietin and its preparation method, the present invention also relates to the preparation and treatment of the mimetic peptide derivatives for the lack of erythropoietin or the lack or deficiency of erythrocytes Use in medicines for characteristic diseases. Background technique [0002] Erythropoietin (hereinafter referred to as EPO) is an active glycoprotein synthesized and secreted by the kidney, 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-typ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/505C07K1/04C07K1/08A61P37/00A61P35/00A61P7/08A61P13/12
Inventor 魏群超郑学敏龚珉周植星徐为人汤立达
Owner 天津天诚新药评价有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com