CN-121974978-A - Targeting ACLY short peptide and application thereof in bacterial infection

Abstract

The invention discloses a targeting ACLY short peptide and application thereof in bacterial infection, belonging to the technical field of biological medicine. According to the invention, three candidate peptides are obtained through molecular docking, virtual screening and the like, and experiments show that the candidate peptide PVP can destroy ACLY-NLRP3 interaction and promote NLRP3 inflammatory corpuscle activation, so that the host defenses against bacterial infection is enhanced. The invention discloses a self-limiting loop of immune-metabolic cross-talk, which positions ACLY-NLRP3 axis as a new therapeutic target of inflammatory small body driving diseases and provides a new short peptide for treating bacterial infection.

Inventors

• GAO CHENGJIANG
• LIU FENG
• YANG YUAN
• ZHAN PENG
• GAO HENG
• Zhuang Wanxin
• ZHAO WENTING
• LIU XUDONG

Assignees

• 山东大学

Dates

Publication Date

20260505

Application Date

20260408

Claims (5)

1. 1. The application of the short peptide in preparing a medicament for resisting bacterial infection is characterized in that the amino acid sequence of the short peptide is any one of SEQ ID NO.1, SEQ ID NO.3 and SEQ ID NO. 5; the bacteria is klebsiella pneumoniae (Klebsiella pneumoniae).
2. 2. The application of the short peptide in preparing anti-inflammatory drugs is characterized in that the amino acid sequence of the short peptide is any one of SEQ ID NO.1, SEQ ID NO.3 and SEQ ID NO. 5; the anti-inflammatory drug is a drug for treating inflammation caused by bacterial infection, and the bacteria is klebsiella pneumoniae (Klebsiella pneumoniae).
3. 3. A short peptide for resisting bacterial infection, which is characterized by comprising any one peptide with an amino acid sequence shown as SEQ ID NO.1, SEQ ID NO.3 and SEQ ID NO. 5.
4. 4. An anti-bacterial infection or anti-inflammatory agent comprising the short peptide of claim 3.
5. 5. The medicament of claim 4, wherein the bacterium is klebsiella pneumoniae (Klebsiella pneumoniae).

Description

Targeting ACLY short peptide and application thereof in bacterial infection Technical Field The invention relates to the technical field of biological medicine, in particular to a targeting ACLY short peptide and application thereof in bacterial infection. Background Inflammatory minibodies are an important component of the innate immune system, mediating caspase-1 activation and maturation of the pro-inflammatory factors IL-1 beta, IL-18, and triggering apoptosis, by recognizing pathogen-associated or damage-associated molecular patterns, playing a key role in host defense and a variety of inflammatory diseases. Among them, NLRP3 inflammatory bodies have become a hot spot in recent years due to their broad response ability to various pathogens and metabolic signals, and close association with chronic inflammation, metabolic diseases, and infectious diseases. The activation of NLRP3 inflammatory corpuscles is strictly regulated, and abnormal activation often leads to excessive inflammatory reaction and tissue injury, whereas insufficient activity may lead to reduced anti-infection capability of a host. Therefore, the search for molecular tools capable of precisely regulating the activation state of NLRP3 inflammatory corpuscles is of great significance for anti-infection and treatment of inflammatory diseases. ATP Citrate Lyase (ACLY) is a key enzyme linking mitochondrial metabolism with cytosolic acetyl-CoA synthesis, and is involved in not only lipid synthesis, but also regulation of epigenetic processes such as histone acetylation. In recent years, ACLY has been found to play a complex role in the inflammatory response, which affects macrophage polarization and inflammatory factor expression through metabolic recombination. However, it is currently unclear whether and how ACLY is directly involved in the regulation of inflammatory bodies, particularly NLRP3 inflammatory bodies. Previous studies by the inventors of the present invention found that ACLY was able to bind directly to the Pyrin domain (PYD) of NLRP3 and inhibit its aggregation and activation, thereby negatively regulating NLRP3 inflammatory small body activation. This finding reveals a non-classical function of metabolic enzymes ACLY in innate immunity, providing a new perspective for understanding immune-metabolic interactions. Based on the above mechanism, if a molecule capable of specifically interfering ACLY with the interaction of NLRP3 could be developed, it would be expected to relieve ACLY inhibition of NLRP3, thereby promoting activation of inflammatory corpuscles at early stage of infection and enhancing host clearance of pathogens. However, there is no report on development of short peptide intervention tools aiming at ACLY-NLRP3 interaction interface, nor is there any study on the use of the short peptides for enhancing the function of a host against bacterial infection. Disclosure of Invention The invention aims to provide a target ACLY short peptide and application thereof in bacterial infection, so as to solve the problems in the prior art, and the screened target ACLY short peptide can destroy ACLY-NLRP3 interaction and promote NLRP3 inflammatory corpuscle activation, thereby enhancing the host defenses against bacterial infection. In order to achieve the above object, the present invention provides the following solutions: The amino acid sequence of the short peptide is any one of SEQ ID NO.1, SEQ ID NO.3 and SEQ ID NO. 5; the bacteria is klebsiella pneumoniae (Klebsiella pneumoniae). The invention also provides application of the short peptide in preparing anti-inflammatory drugs, wherein the amino acid sequence of the short peptide is any one of SEQ ID NO.1, SEQ ID NO.3 and SEQ ID NO. 5; the anti-inflammatory drug is a drug for treating inflammation caused by bacterial infection, and the bacteria is klebsiella pneumoniae (Klebsiella pneumoniae). The invention also provides a short peptide for resisting bacterial infection, which comprises any one peptide with an amino acid sequence shown as SEQ ID NO.1, SEQ ID NO.3 and SEQ ID NO. 5. The invention also provides an anti-bacterial infection or anti-inflammatory drug comprising the short peptide. The bacteria is klebsiella pneumoniae (Klebsiella pneumoniae). The invention discloses the following technical effects: The present invention developed a short peptide that disrupts ACLY-NLRP3 interactions and promotes NLRP3 inflammatory body activation, thereby enhancing host defenses against bacterial infection. The invention discloses a self-limiting loop of immune-metabolic cross-talk, which positions ACLY-NLRP3 axis as a new therapeutic target of inflammatory small body driving diseases and provides a new short peptide for treating bacterial infection. Drawings In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the embodiments will be briefly described below, and it is obvious th