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

HRP5 analogue and preparation method thereof

An amino acid and sequence technology, applied in the field of medicine, can solve problems such as toxicity and high killing activity of pathogens

Active Publication Date: 2015-02-18
SHANGHAI INST OF PHARMA IND CO LTD +2
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, natural cationic antimicrobial peptides are not perfect. Some antimicrobial peptides have certain toxicity to eukaryotes, and their high killing activity on pathogens is often accompanied by hemolysis to eukaryotes.

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
  • HRP5 analogue and preparation method thereof
  • HRP5 analogue and preparation method thereof
  • HRP5 analogue and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Embodiment 1: Preparation and purification of AMP-1

[0069] Sequence: Lys-Arg-Leu-Phe-Lys-Lys-Leu-Leu-Lys-Tyr-Leu-Arg-Lys-Phe-NH 2 (SEQ ID NO:3)

[0070] (1) Materials and reagents

[0071] Rink Amide MBHA resin, substitution value 0.41mmol / g.

[0072] The amino acids to be protected are Fmoc-L-Arg(Pbf)-OH, Fmoc-L-Leu-OH, Fmoc-L-Lys(Boc)-OH, Fmoc-L-Phe-OH and Fmoc-L-Tyr (tBu)-OH.

[0073] Reagents: HOBt, DIC, DMF, piperidine.

[0074] (2) Instrument

[0075] PSI300 peptide synthesizer, Waters600 semi-preparative high performance liquid chromatography, magnetic stirrer.

[0076] (3) Operation steps (take 0.25mmol as an example)

[0077] a. Solid-phase chemical synthesis of peptides

[0078] Weigh 0.61g of Rink Amide MBHA resin, put it in the reactor of the peptide synthesizer, add 10mL of DMF, soak for 2h, then add 15mL of 20% PIP / DMF solution, mix for 30min to remove the amino protecting agent, and wash the resin 7 times with DMF , then add 387.4mg Fmoc-L-Phe-...

Embodiment 2

[0092] Example 2: Preparation and purification of HRP5 analogues in Table 4

[0093] (1) Materials and reagents

[0094] Rink Amide MBHA resin, substitution value 0.41mmol / g.

[0095] Desired protected amino acids Fmoc-L-Arg(Pbf)-OH, Fmoc-D-Arg(Pbf)-OH, Fmoc-L-Leu-OH, Fmoc-L-HoR(Pbf)-OH, Fmoc-L -Lys(Boc)-OH, Fmoc-D-Lys(Boc)-OH, Fmoc-L-Phe-OH, Fmoc-D-Phe-OH, Fmoc-L-Tyr(tBu)-OH, Fmoc-L- Ile-OH, Fmoc-L-Nle-OH, Fmoc-L-Thi-OH and Fmoc-L-Aib-OH.

[0096] Reagents: HOBt, DIC, DMF, piperidine.

[0097] (2) Instrument

[0098] PSI300 peptide synthesizer, Waters600 semi-preparative high performance liquid chromatography, magnetic stirrer.

[0099] (3) Operation steps (take 0.25mmol as an example)

[0100] The polypeptides in Table 4 were prepared and purified in a manner similar to the steps a-c in Example 1, and the fractions with a purity greater than 99% were collected and then concentrated to dryness at 50°C under reduced pressure. The ESI-MS measured values ​​are shown in Ta...

Embodiment 3

[0103] Example 3: Preparation and purification of cyclic peptide AMP-13

[0104] sequence: (SEQ ID NO: 15)

[0105] (1) Materials and reagents

[0106] Rink Amide MBHA resin, substitution value 0.41mmol / g.

[0107] The amino acids to be protected are Fmoc-L-Arg(Pbf)-OH, Fmoc-L-Leu-OH, Fmoc-L-Lys(Boc)-OH, Fmoc-L-Phe-OH, Fmoc-L-Tyr (tBu)-OH and Fmoc-L-Cys(Trt)-OH.

[0108] Reagents: HOBt, DIC, DMF, piperidine, 30% H 2 o 2 .

[0109] (2) Instrument

[0110] PSI300 peptide synthesizer, Waters600 semi-preparative high performance liquid chromatography, magnetic stirrer.

[0111] (3) Operation steps

[0112] a. Prepared and purified by a method similar to the operation steps a-c in Example 1. Cys-NH 2 ), the fractions with a purity greater than 99% were collected, and then concentrated to dryness at 50°C under reduced pressure. As determined by ESI-MS, the molecular weight of the peptide is 2086.24, and the theoretical value is 2086.72.

[0113] b. Intramolecular disul...

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 the field of medicines, and particularly relates to an HRP5 analogue and a preparation method thereof. The general formula of the amino acid sequence of the HRP5 analogue is as shown in SEQ ID NO:2: Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Leu-Xaa11-Lys-Tyr-Leu-Arg-Xaa16-Xaa17-Xaa18. The activity determination of the HRP5 analogue in vitro shows that the polypeptide provided by the invention has significant sterilization effects on gram positive bacteria, gram negative bacteria and fungi, also has significant sterilization effects on drug-resistant gram positive bacteria, drug-resistant gram negative bacteria and drug-resistant fungi clinically isolated, and has the characteristics of being wide in spectrum and high in effects.

Description

[0001] This application is a divisional application with the application number 201110116643.9, the filing date is May 6, 2011, and the invention title is "a group of novel HRP5 analogues and their preparation methods". technical field [0002] The invention belongs to the field of medicine, and in particular relates to a group of novel HRP5 analogues with broad-spectrum antibacterial activity and a preparation method thereof. Background technique [0003] Since the discovery of penicillin, antibiotics have been a powerful weapon for humans to treat pathogenic microbial infections. However, with the abuse of traditional antibiotics, more and more pathogenic bacteria have begun to develop resistance to traditional antibiotics. Therefore, it is urgent to find a new class of antibacterial drugs. Use instead of antibiotics. [0004] Cationic antimicrobial peptides are cationic (rich in arginine and lysine) polypeptides produced by plants and animals, generally composed of 12-50 ...

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): C07K7/08C07K1/10C07K1/06C07K1/02A61K38/10A61P31/04A61P31/10
CPCY02P20/55
Inventor 冯军路建光张喜全徐宏江吴勇朱裕辉杨洁
Owner SHANGHAI INST OF PHARMA IND CO LTD
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