CN-121971585-A - Application of micromolecular drug ATWLPPR PEPTIDE TFA in resisting mycobacterium bovis infection

Abstract

The invention discloses an application of a small molecular medicine ATWLPPR PEPTIDE TFA in resisting mycobacterium bovis infection, belongs to the field of biological medicine, and relates to a small molecular medicine ATWLPPR PEPTIDE TFA which is an agonist of a target host factor NRP1, and then we explore the inhibition effect of ATWLPPR PEPTIDE TFA treatment on mycobacterium bovis in vitro and in vivo. In vitro bacterial load titration results showed that ATWLPPR PEPTIDE TFA treatment was able to demonstrate a dose-dependent inhibition of mycobacterium bovis adhesion to a549 cells. The experimental result of the mice shows that ATWLPPR PEPTIDE TFA treatment can inhibit the mice from infecting mycobacterium bovis, effectively lighten the pathological damage of the lung tissues of the mice, and provides a brand new direction for the prevention and control of mycobacterium bovis.

Inventors

• QU MENGJIN
• HE XIJUN
• WANG GUANGWEN
• ZHANG XIANFENG

Assignees

• 中国农业科学院哈尔滨兽医研究所（中国动物卫生与流行病学中心哈尔滨分中心）

Dates

Publication Date

20260505

Application Date

20260225

Claims (2)

1. 1. Use of small molecule drug ATWLPPR PEPTIDE TFA in the preparation of a medicament for combating mycobacterium bovis infection.
2. 2. Use of a small molecule drug ATWLPPR PEPTIDE TFA for inhibiting mycobacterium bovis for non-disease treatment purposes.

Description

Application of micromolecular drug ATWLPPR PEPTIDE TFA in resisting mycobacterium bovis infection Technical Field The invention belongs to the field of biological medicine, and in particular relates to application of a small molecule drug ATWLPPR PEPTIDE TFA in resisting mycobacterium bovis infection. Background Mycobacterium bovis (Mycobacterium bovis, M.bovis) is an important zoonotic pathogen that infects livestock and transmits across species to humans, severely threatening the sustainable development of the livestock industry and public health safety. At present, mycobacterium bovis prevention and control mainly depends on vaccine immunization, but the only BCG protection effect of BCG vaccine obtained by batch is very limited, and development of novel intervention means is urgently needed. In response to this need, we have proposed an innovative strategy to block the invasion process of Mycobacterium bovis by looking for small molecule drugs targeting host key factors. The small molecule drug ATWLPPR PEPTIDE TFA is a selective neuropilin-1 (NRP 1) inhibitor (structure shown in FIG. 1). NRP1 is a single transmembrane glycoprotein receptor comprising two CUB domains at the N-terminus (involved in specific protein recognition), two clotting factor FV/VIII homology domains (primary ligand binding regions), a C-terminal MAM domain (responsible for receptor dimerization), a transmembrane domain, and an intracellular domain (signal transduction engagement). Disclosure of Invention The invention aims to provide a novel application of a small molecule drug ATWLPPR PEPTIDE TFA in inhibiting mycobacterium bovis. The technical scheme of the invention is that the micromolecular drug ATWLPPR PEPTIDE TFA is used for preparing drugs for resisting mycobacterium bovis infection. Use of a small molecule drug ATWLPPR PEPTIDE TFA for inhibiting mycobacterium bovis for non-disease treatment purposes. Compared with the prior art, the invention has the following beneficial effects: We explored the inhibition of Mycobacterium bovis by ATWLPPR PEPTIDE TFA treatments in vitro and in vivo. In vitro bacterial load titration results showed that ATWLPPR PEPTIDE TFA treatment was able to demonstrate a dose-dependent inhibition of mycobacterium bovis adhesion to a549 cells. The experimental result of the mice shows that ATWLPPR PEPTIDE TFA treatment can inhibit the mice from infecting mycobacterium bovis, effectively lighten the pathological damage of the lung tissues of the mice, and provides a brand new direction for the prevention and control of mycobacterium bovis. Drawings FIG. 1 is a chemical formula of a small molecule compound ATWLPPR PEPTIDE TFA that targets NRP 1. FIG. 2 is a graph showing the effect of ATWLPPR PEPTIDE TFA at various concentrations on A549 cell viability. FIG. 3 is a ATWLPPR PEPTIDE TFA treatment inhibiting Mycobacterium bovis adhesion A549 cells. Fig. 4 is a schematic diagram of an animal experiment. FIG. 5 shows the effect of ATWLPPR PEPTIDE TFA treatment on the individual tissue organs of mice. Figure 6 is ATWLPPR PEPTIDE TFA treatment to reduce bacterial load in the lungs and spleen of mice. FIG. 7 is a ATWLPPR PEPTIDE TFA treatment for alleviating pathological lesions in the lungs of mice. Detailed Description The experimental methods in the following examples are conventional methods unless otherwise specified. The test materials used in the examples described below, unless otherwise specified, were purchased from commercial sources. Experimental materials A549 cells (human lung cancer epithelial cells) were purchased from ATCC, and small molecule compound ATWLPPR PEPTIDE TFA (FIG. 1) was purchased from MCE company (product number HY-P1663A) and dissolved in DMSO to prepare 100 mM stock solution, which was stored in aliquots frozen at-80 ℃. Mycobacterium bovis used in this experiment was strain C68004. The strain C68004 is a clinical strain separated from tuberculosis focus of tuberculosis positive cattle in Beijing area in 1953, and is stored in Chinese veterinary medicine monitoring institute. The related experiments of the mycobacterium bovis related to the experiment are all carried out in P3 class laboratories of Harbin veterinary institute of China academy of agricultural sciences. Example 1 determination of the Effect of different concentrations of ATWLPPR PEPTIDE TFA on A549 cell viability Using CELLTITER GLO cell viability kit A549 cell suspension was plated in 96-well plates, placed in a 37℃cell incubator (5% CO 2) for culturing, 100 mM ATWLPPR Peptide TFA stock solution was diluted to 25 and 10. Mu.M working solutions with F-12K medium (0.3% BSA), then 150. Mu.L of ATWLPPR PEPTIDE TFA working solution and DMSO-containing diluent (three wells each) of the above different concentrations were added to 96-well plates with A549 cell densities of 95%, after incubation in a 37℃cell incubator for 24h, 100. Mu. L CELLTITER-Glo solution (G7572, promega) was added to each well for incubation in a 37℃i