CN-120518705-B - Polypeptide compound and preparation method and application thereof

Abstract

The invention discloses a polypeptide compound and a preparation method and application thereof, and belongs to the technical field of marine source active substances. According to the invention, two polypeptide compounds which obviously inhibit IL-1 beta secretion driven by NLRP3 inflammatory corpuscles are separated from a fungal Simplicillium sp.HDN17-843 liquid fermentation product derived from a Antarctic marine sediment sample. The research shows that the polypeptide compound has obvious anti-inflammatory activity, which indicates that the polypeptide compound has the potential of further developing into novel anti-inflammatory drugs.

Inventors

• LI DEHAI
• WANG ZHENGJIE
• JIANG YUQI
• ZHU TIANJIAO
• CHE QIAN
• HUANG LUYAO

Assignees

• 中国海洋大学

Dates

Publication Date

20260512

Application Date

20250723

Claims (1)

1. 1. The application of the polypeptide compound in preparing anti-inflammatory medicaments is disclosed, wherein the structural formula of the polypeptide compound is shown as formula I or formula II: ; the polypeptide compound is prepared by fermenting and culturing microorganisms, wherein the microorganisms are Simplicillium sp, HDN17-843, the preservation number is CCTCC No. M2023673, the preservation date is 2023, 05 month 04, and the preservation unit is China center for type culture Collection.

Description

Polypeptide compound and preparation method and application thereof Technical Field The invention belongs to the technical field of marine source active substances, and particularly relates to a polypeptide compound, a preparation method and application thereof. Background NLRP3 inflammatory corpuscles are an intracellular polyprotein complex that plays a key role in the inflammatory response. Its core components include NLRP3 protein, apoptosis-related speckle protein (ASC) and cysteine protease-1 (Caspase-1). Activation of NLRP3 inflammatory corpuscles usually requires two signals, namely firstly, that the cells receive a start signal through Toll-like receptors and the like to enable the cells to be in a pre-activated state, and then, activation signals such as extracellular potassium ion outflow, lysosome injury and the like further activate NLRP3 proteins to recruit ASC and Caspase-1 to form a complex. Activated Caspase-1 cleaves and matures the precursor proteins of interleukin-1 beta (IL-1 beta) and interleukin-18 (IL-18), triggering an inflammatory response. Under physiological conditions, NLRP3 inflammatory bodies help clear pathogens and maintain immune homeostasis. However, under pathological conditions, its abnormal activation can lead to a variety of diseases. For example, rheumatoid arthritis, alzheimer's disease, diabetes, cancer, cardiovascular disease, and the like. Therefore, the development of NLRP3 inhibitors has important significance for preventing and treating rheumatoid arthritis, alzheimer disease, diabetes, cancer, cardiovascular diseases and the like. Disclosure of Invention The invention aims to provide a polypeptide compound, and a preparation method and specific application of the polypeptide compound, so as to make up the defects of the prior art. In order to achieve the purpose, the invention adopts the following specific technical scheme: A polypeptide compound has a structural formula shown in formula I or formula II: A formula I; Formula II. The preparation method of the polypeptide compound comprises the steps of preparing a fermentation crude extract by microbial fermentation culture, and separating and purifying the fermentation crude extract by adopting methods such as C-18 ODS reversed phase column chromatography, semi-preparative HPLC and the like. The microorganism is specifically fungus HDN17-843 Simplicillium sp, HDN17-843, the preservation number is CCTCC No. M2023673, the preservation date is 2023, 05 and 04, the preservation organization is China center for type culture Collection, the preservation address is eight-path 299 of university of Wuhan student, university of Wuhan, hubei province, and the post code 430072. Further, the preparation method specifically comprises the following steps: (1) Taking a proper amount of fungi Simplicillium sp, HDN17-843 according to a conventional method for culturing microorganisms, inoculating to a fungus 2# liquid culture medium, and standing at room temperature for culturing to obtain a fermentation product; (2) Standing at room temperature for several days, processing the fermented product, adding equal volume of ethyl acetate into the fermented liquid, repeatedly extracting for three times, concentrating under reduced pressure to obtain extract, crushing mycelium, adding equal volume of methanol, ultrasonic extracting for several times, concentrating to obtain extract, mixing the two extracts; (3) And (3) performing C-18 ODS reversed phase column chromatography by taking methanol-water as a mobile phase on the extract prepared in the step (2), and performing reversed phase semi-preparation high performance liquid chromatography (acetonitrile: water=50:50) after gradient elution to obtain the polypeptide compound shown in the formula I or the formula II. The polypeptide compound can obviously inhibit IL-1 beta secretion driven by NLRP3 inflammation corpuscle, and the application thereof in preparing an IL-1 beta secretion product for inhibiting NLRP3 inflammation corpuscle. The application of the polypeptide compound in preparing anti-inflammatory drugs. Compared with the prior art, the invention has the advantages that: According to the invention, two polypeptide compounds which obviously inhibit IL-1 beta secretion driven by NLRP3 inflammatory corpuscles are separated from a fungal Simplicillium sp. The research shows that the polypeptide compound has obvious anti-inflammatory activity, which indicates that the polypeptide compound has the potential of further developing into novel anti-inflammatory drugs. Drawings FIG. 1 is a graph showing the results of inhibition of IL-1β by Compound I at various concentrations. FIG. 2 is a graph showing the results of inhibition of IL-1β by Compound II at various concentrations. Detailed Description The invention is further illustrated and described below by means of specific embodiments in connection with the accompanying drawings. EXAMPLE 1 fermentative production and separation