阅读说明：本技术 一种共组装氨基酸抗菌复合水凝胶 (Co-assembled amino acid antibacterial composite hydrogel ) 是由 谢燕燕 冯佳媛 秦晓彤 钟成 于 2020-06-01 设计创作，主要内容包括：本发明提供了一种共组装氨基酸抗菌复合水凝胶。该体系由Fmoc-Leu-OH和Fmoc-Lys-OH组成,其中,Leu为亮氨酸,Lys为赖氨酸。本发明氨基酸复合水凝胶具有良好的共组装能力,且本发明对革兰氏阳性菌金黄葡萄球菌、枯草芽孢杆菌、李斯特菌和革兰氏阴性菌大肠杆菌有抑制效果。(The invention provides a co-assembled amino acid antibacterial composite hydrogel. The system consists of Fmoc-Leu-OH and Fmoc-Lys-OH, wherein Leu is leucine, and Lys is lysine. The amino acid composite hydrogel has good co-assembly capacity, and has an inhibition effect on gram-positive bacteria staphylococcus aureus, bacillus subtilis, listeria and gram-negative bacteria escherichia coli.)

1. The co-assembled amino acid antibacterial composite hydrogel is characterized in that Fmoc-Leu-OH and Fmoc-Lys-OH are co-assembled to form the antibacterial hydrogel, and the monomer structure of the antibacterial hydrogel is as follows:

wherein Fmoc is fluorenylmethoxycarbonyl, Leu is leucine, and Lys is lysine.

2. The composite amino acid hydrogel of claim 1, wherein the hydrophobic amino acid residue of the co-assembled antimicrobial hydrogel is Leu.

3. The preparation method of the co-assembled antibacterial hydrogel according to claim 1, wherein the co-assembled amino acids are respectively dispersed in a PB (pH 7.2) solution to prepare a 60mM solution, ultrasonic treatment is carried out for 10-30 s to ensure that the amino acids are uniformly dispersed, a dispersed amino acid suspension is heated in a water bath kettle at 80 ℃ until the solution is completely clarified, then two solutions with certain volumes are respectively diluted, mixed according to a proportion after dilution, naturally cooled at room temperature, kept stand, and assembled to form the hydrogel, wherein the micro-morphology of the hydrogel is spiral nanofibers with the diameter of about 100 nm.

4. A composition comprising the co-assembled antibacterial hydrogel according to claim 1, wherein the co-assembled antibacterial hydrogel is co-assembled into a 3:1 colloid at the concentrations of 45mM and 15mM for dissolving Fmoc-Leu-OH and Fmoc-Lys-OH powders, and has good inhibitory activity on the growth of gram-positive bacteria and gram-negative bacteria.

5. The composition of claim 4, wherein the gram positive bacterium is Staphylococcus aureus S.aureus, Bacillus subtilis, Listeria, and the gram negative bacterium is Escherichia coli E.coli.

Technical Field

The invention relates to the field of polypeptide co-assembly, in particular to an amino acid antibacterial composite hydrogel.

Background

Bacterial infections are one of the major public health safety problems facing the world today, with up to tens of millions of deaths worldwide due to bacterial infections each year. Although antibiotics are still the most effective bacteriostasis method at present, the problem of bacterial drug resistance caused by overuse of antibiotics is increasingly prominent, and development of a brand-new antibacterial strategy is not slow enough. The antibacterial hydrogel can solve the problems of high toxicity, drug resistance, multiple administration and the like of the traditional antibiotic injection treatment, is widely concerned and has important research significance for treating bacterial infection diseases.

The amino acid composite hydrogel synthesized based on supramolecular co-assembly is combined by non-covalent bonds such as hydrogen bonds, pi-pi stacking interaction, hydrophobic acting force and the like, has good biocompatibility, low cytotoxicity and difficult allergic reaction, and also has the characteristics of degradability, molecular recognition, stimulus response and the like, so that the amino acid composite hydrogel has a wide development space in the fields of tissue engineering, drug delivery, wound dressing and the like.

Currently, a variety of complex amino acid hydrogels are developed and applied in a variety of ways including bioscaffolds, drug loading, hemostasis, and antisepsis. However, at the present stage, people do not know the relationship between the structure and the activity of the compound amino acid deeply enough, and how to develop an efficient and high-selectivity antibacterial drug through the modification and design of amino acid molecules is also a difficult problem.

Disclosure of Invention

The invention aims to provide a co-assembled amino acid hydrogel which has good co-assembly capacity, has an inhibition effect on gram-positive bacteria staphylococcus aureus, bacillus subtilis and listeria and has an inhibition effect on gram-negative bacteria escherichia coli.

The co-assembled amino acid hydrogel is characterized in that the composite amino acid hydrogel is assembled by Fmoc-Leu-OH and Fmoc-Lys-OH, and the monomer structure is as follows:

wherein Fmoc is fluorenylmethyloxycarbonyl acyl, Leu is leucine, and Lys is lysine.

In the above co-assembled complex amino acid hydrogel structure, the hydrophobic amino acid residue is Leu.

The composite amino acid is co-assembled by a heating and cooling method, and the diameter of the composite amino acid is about 100 nm.

In another aspect of the invention, a composition is provided, which comprises the above-described composite amino acid hydrogel.

In the composition, the co-assembled antibacterial hydrogel is co-assembled into a 3:1 colloid in the same volume with the dissolving concentration of 45mM and 15mM in Fmoc-Leu-OH and Fmoc-Lys-OH powder, and has good inhibition on the growth of gram-positive bacteria.

The composition of claim 5, wherein the gram negative bacteria are E.coli and the gram positive bacteria are S.aureus, B.subtilis, Listeria.

The invention has the beneficial effects that:

(1) compared with the traditional hydrogel, the co-assembled amino acid composite hydrogel has good bacteriostatic effect on gram-positive bacteria staphylococcus aureus and bacillus subtilis and has good biocompatibility.

(2) The preparation method adopted by the invention has the advantages of simple system, rapid reaction and no need of additionally adding auxiliary gelling factors. Drawings

FIG. 1 is a diagram of amino acid composite hydrogel of the present invention

FIG. 2 is a transmission electron microscope characterization chart of the amino acid composite hydrogel of the invention

FIG. 3 is a graph showing the results of the survival rate characterization of Staphylococcus aureus S.aeurs, Bacillus subtilis B.subtilis, Listeria, Escherichia coli E.coli in the presence of amino acid composite hydrogel

Detailed Description

The present invention will be described below with reference to specific embodiments, but the present invention is not limited to these.

The experimental methods used in the following examples are all conventional methods unless otherwise specified; reagents, biomaterials, etc. used in the following examples are commercially available unless otherwise specified.

Fmoc-Leu-OH and Fmoc-Lys-OH powders used in the following examples were synthesized by Gill Biochemical Co., Ltd, Shanghai. The preparation method of the PB solution with the pH of 7.4 comprises the steps of weighing 71.6g of disodium hydrogen phosphate dodecahydrate and 31.2g of monopotassium phosphate dihydrate to achieve a constant volume of 1000 mL. 81ml of disodium hydrogen phosphate dodecahydrate is mixed with 19ml of potassium dihydrogen phosphate dihydrate to prepare the mixture.