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Tachyplesin I antibacterial peptide derivative as well as preparation method and application thereof

A technology of antibacterial peptides and derivatives, applied in the field of biomedicine, can solve the problem of limited sources of limulus, and achieve the effects of simple structure, wide bactericidal spectrum and high activity

Active Publication Date: 2021-11-09
QINGDAO UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the natural source of tachyplesin is very limited, and the main way to obtain it is chemical synthesis. Therefore, the design and synthesis of Tachyplesin I derivatives with diverse structures, and the discovery of lead compounds with better activity, broad bactericidal spectrum, and simpler structure are important for the development of new broad-spectrum Antimicrobial peptides are very important

Method used

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  • Tachyplesin I antibacterial peptide derivative as well as preparation method and application thereof
  • Tachyplesin I antibacterial peptide derivative as well as preparation method and application thereof
  • Tachyplesin I antibacterial peptide derivative as well as preparation method and application thereof

Examples

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preparation example Construction

[0043] The synthetic method of above-mentioned antibacterial peptide derivative, comprises the following steps:

[0044] (1) Compounds TD-1c, TD-2c, TD-3c, TD-4c, and TD-5c without disulfide bonds were synthesized by solid-phase synthesis method, using Fmoc-amino resin as solid-phase carrier, and using polypeptide solid-phase The synthesis method is to sequentially couple the required amino acids from the C-terminal to the N-terminal according to the peptide sequence to obtain a linear fully protected peptide resin. Carry out cracking subsequently, lysate is selected the mixed solution of TFA, thioanisole, anisole and water volume ratio 90:5:2.5:2.5, and the amount of lysate is to use 8-20mL of lysate per 1g peptide resin, preferably 10mL, the lysis is carried out at room temperature, the lysis time is 1.5-3h, preferably 2h, after the lysis is completed, blow off excess trifluoroacetic acid with nitrogen, add glacial ether, a white solid is precipitated, the solid after centrifu...

Embodiment 1

[0049] Example 1: Synthesis of linear polypeptide TD-1c containing 0 pairs of disulfide bonds

[0050] Accurately weigh 500mg of Rink Amide resin (0.38mmol) with a degree of substitution of 0.76mmol / g in a solid-phase synthesis reactor, add DCM to swell for 20min, then add 20% piperidine / DMF solution twice to remove the Fmoc protecting group , remove for 5 minutes for the first time, remove for 20 minutes for the second time, wash with DMF, DCM and methanol for 3 to 5 times, and drain. Add pre-mixed and fully activated Fmoc-Arg(pbf)-OH (0.38mmol), HoBt (0.46mmol), DIC (0.46mmol), DMF (5ml) into the reactor, react at room temperature for 1h, wash with DMF for 3 ~5 times, drained, add 5mL of blocking reagent (acetic anhydride:DIPEA molar ratio is 1:1) into the reactor, react at room temperature for 2h, wash with DCM, methanol and DMF respectively for 3~5 times, repeat the above-mentioned Fmoc removal The removal step and the post-washing step, and then continue to add Fmoc-Trp(...

Embodiment 2

[0051] Example 2: Synthesis of linear polypeptide TD-1 containing 2 pairs of disulfide bonds

[0052] Accurately weigh 500mg of Rink Amide resin (0.38mmol) with a degree of substitution of 0.76mmol / g in a solid-phase synthesis reactor, add DCM to swell for 20min, then add 20% piperidine / DMF solution twice to remove the Fmoc protecting group , remove for 5 minutes for the first time, remove for 20 minutes for the second time, wash with DMF, DCM and methanol for 3 to 5 times, and drain. Add pre-mixed and fully dissolved Fmoc-Arg(pbf)-OH (0.38mmol), HoBt (0.46mmol), DIC (0.46mmol), DMF (5ml), react at room temperature for 1h, wash with DMF for 3 ~5 times, drained, add 5mL of blocking reagent (acetic anhydride:DIPEA molar ratio is 1:1) into the reactor, react at room temperature for 2h, wash with DCM, methanol and DMF respectively for 3~5 times, repeat the above-mentioned Fmoc removal The removal step and the post-washing step, and then continue to add Fmoc-Trp(Boc)-OH (0.38mmol)...

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Abstract

The invention discloses a group of Tachyplesin I antibacterial peptide derivatives as well as a preparation method and application thereof. The Tachyplesin I antibacterial peptide derivatives have the following structural general formula: wherein a fragment A, a fragment B and a fragment C are respectively and independently selected from any one of the following peptide fragments:-Trp-Cys-Phe-Arg-, -Val-Cys-Tyr-Arg-and -Ile-Cys-Tyr-Arg-; and 0 pair, 1 pair or 2 pairs of disulfide bonds are formed between the third Cys and the sixteenth Cys and between the seventh Cys and the twelfth Cys. According to the invention, a derivative compound library of natural Tachyplesin I is enriched in a manner of replacing and combining active fragments again and changing the number of disulfide bonds, and a potential antibacterial drug with excellent antibacterial activity is screened from the derivative compound library, so that the derivative compound library has advantages of high activity, wide bactericidal spectrum and simple structure, and is of great significance for developing novel broad-spectrum antibacterial peptides.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a group of Tachyplesin I antimicrobial peptide derivatives and a preparation method and application thereof. Background technique [0002] Tachyplesin I is a small molecular polypeptide isolated and purified from the blood cells of Limulus chinensis, an ancient marine organism. It is an amphipathic peptide consisting of 17 amino acid residues, and two disulfide bonds restrict it to antiparallel β-hairpin structure. A large number of studies have found that Tachyplesin I has various biological activities such as antibacterial, antiviral, and antitumor. A new type of peptide drug has attracted much attention. It has spectrum antibacterial activity against Gram-positive bacteria, Gram-negative bacteria and fungi, and its minimum inhibitory concentration (MIC) can reach 0.3-13 μmol / L (Tam, J.P.; Lu, Y.A.; Yang, J.L. Biochem Biophys Res Commun 2000, 267, 783-90). A number of s...

Claims

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Application Information

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IPC IPC(8): C07K7/08C07K1/20C07K1/06C07K1/04A61K38/10A61P31/04A61P31/10
CPCC07K7/08A61P31/04A61P31/10A61K38/00Y02P20/55
Inventor 张传亮
Owner QINGDAO UNIV OF SCI & TECH
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