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HRP5 analogues 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: 2015-01-21
SHANGHAI INST OF PHARMA IND +2
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  • 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

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  • HRP5 analogues and preparation method thereof
  • HRP5 analogues and preparation method thereof
  • HRP5 analogues and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] Embodiment 1: Preparation and purification of AMP-1

[0068] Sequence: Lys-Arg-Leu-Phe-Lys-Lys-Leu-Leu-Lys-Tyr-Leu-Arg-Lys-Phe-NH2 (SEQ ID NO: 3)

[0069] (1) Materials and reagents

[0070] Rink Amide MBHA resin, substitution value 0.41mmol / g.

[0071] 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.

[0072] Reagents: HOBt, DIC, DMF, piperidine.

[0073] (2) Instrument

[0074] PSI300 peptide synthesizer, Waters600 semi-preparative high performance liquid chromatography, magnetic stirrer.

[0075] (3) Operation steps (take 0.25mmol as an example)

[0076] a. Solid-phase chemical synthesis of peptides

[0077] 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-O...

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...

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Abstract

The invention belongs to the field of medicines and in particular relates to HRP5 analogues and a preparation method thereof. The general formulas of amino acid sequences of the HRP5 analogues disclosed by the invention are shown in SEQ ID NO:2, namely Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Leu-Xaa11-Lys-Tyr-Leu-Arg-Xaa16-Xaa17-Xaa18. The in-vitro activity measurement proves that the polypeptides provided by the invention have obvious effects of killing gram-positive bacteria, Gram-negative bacteria and fungi, also have obvious effects of killing clinically separated drug-resistant gram-positive bacteria, drug-resistant gram-negative bacteria and drug-resistant fungi and have the characteristics of broad spectrum and high efficiency.

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

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Application Information

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IPC IPC(8): C07K14/47C07K1/06C07K1/04A61K38/17A61P31/04A61P31/10
CPCY02P20/55C07K14/47A61K38/00
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
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