CN-121248747-B - Antibacterial peptide mutant and application thereof

Abstract

The invention discloses an antibacterial peptide mutant and application thereof, wherein the amino acid sequence of the antibacterial peptide mutant is shown as SEQ ID NO. 1. According to the invention, 10 potential candidate peptides are obtained by optimizing the sequence of the cellular peptide, and the antibacterial activity and the hemolytic property of the candidate peptides are evaluated to obtain the antibacterial peptide with high activity, low toxicity and long half-life. The antibacterial peptide molecule with high antibacterial activity obtained by the invention not only remarkably reduces toxicity in a host, but also greatly improves in vivo stability, thereby becoming a high-quality antibacterial peptide candidate molecule with high efficiency, safety and stability, and effectively increasing clinical application potential thereof.

Inventors

• JIANG YINGZHI
• XIE PEILIN
• Yao Lantian
• DU JUAN
• CHENG XIAOYUE

Assignees

• 香港中文大学（深圳）

Dates

Publication Date

20260512

Application Date

20250923

Claims (6)

1. 1. The antibacterial peptide mutant is characterized in that the amino acid sequence of the antibacterial peptide mutant is shown as SEQ ID NO. 1.
2. 2. The antimicrobial peptide mutant according to claim 1, wherein the antimicrobial peptide mutant has a minimum inhibitory concentration of 15 μm.
3. 3. Use of the antibacterial peptide mutant according to claim 1 for the preparation of an anti-e.
4. 4. The use according to claim 3, wherein the anti-e.coli product is an anti-e.coli drug.
5. 5. The use according to claim 4, wherein the anti-e.coli medicament further comprises pharmaceutically acceptable excipients.
6. 6. The use according to claim 4, wherein the medicament is any one of a water-impregnated, powder, lotion, tincture, oil, ointment, plaster or aerosol.

Description

Antibacterial peptide mutant and application thereof Technical Field The invention relates to the technical field of antibacterial peptides, in particular to an antibacterial peptide mutant and application thereof. Background Antibacterial peptides (Antimicrobial Peptides, AMPs) are important candidates as antibiotic alternatives because of their ability to rapidly destroy microbial cell membranes and difficulty in inducing resistance. However, naturally or artificially designed antimicrobial peptides are often limited by "high activity-high toxicity" or "low toxicity-low activity" trade-offs and have short half-lives due to their susceptibility to degradation by proteases, resulting in insufficient drug formation. The antibacterial peptide is a kind of short peptide naturally existing in animals, plants and microorganisms, has important functions of broad-spectrum antibacterial, antifungal, antiviral and the like, and has important strategic significance in the development of anti-infective drugs because the antibacterial peptide mainly plays a role in destroying a microbial membrane structure or regulating immune response and is not easy to induce bacteria to generate drug resistance. However, most of the current naturally or artificially designed antibacterial peptides still face significant limitations in vivo applications, mainly in terms of high toxicity, poor stability, insufficient pharmacokinetic properties, and the like. For example, many peptides with high antimicrobial activity have strong hemolysis or toxic and side effects on mammalian cells at the same time, which causes a major potential safety hazard for in vivo use, while another part of peptides, although less toxic, have insufficient activity and cannot reach an effective level of bacteriostasis. Meanwhile, the antibacterial peptide is extremely easy to be degraded by protease in vivo, has short half-life period, is difficult to maintain effective concentration, and further affects the treatment effect. These factors significantly limit the progress of the pharmacologic process of the antimicrobial peptide. The existing antibacterial peptide optimization design method mostly aims at improving antibacterial activity, and lacks systematic consideration on key indexes such as toxicity, half-life and the like, so that the generated candidate peptide has poor comprehensive performance. Some researches try to predict the activity or toxicity of the peptide by adopting a machine learning or deep learning model, but the optimization process still fails to realize balance and synergy among multiple indexes, and the screening efficiency and screening quality of the candidate peptide still have defects. The current antibacterial peptide optimization method based on rule design or single-point mutation strategy often cannot effectively model nonlinear coupling relations among high-dimensional physicochemical features contained in sequences, the optimization process is easy to be in local optimization, global searching capability is lacking, and performance bottlenecks exist in the aspects of activity, toxicity or stability of the generated peptide sequences. Disclosure of Invention Aiming at the defects of the prior art, the invention provides an antibacterial peptide mutant and application thereof, wherein the antibacterial peptide mutant remarkably reduces toxicity to a host and prolongs in-vivo half-life while improving antibacterial activity by a multi-objective calculation optimization method, and a candidate peptide sequence with more patent medicine prospect is obtained. The invention provides an antibacterial peptide mutant, the amino acid sequence of which is shown as SEQ ID NO.1 (PIGALMLKLHTGFPCMICAIKRKRVI), and the antibacterial peptide mutant protein has the characteristics of high activity, low toxicity and long half-life. Further, the minimum inhibitory concentration of the antibacterial peptide mutant is 15 mu M. The invention also provides an expression cassette or a recombinant vector, which can express the antibacterial peptide mutant. The invention also provides a recombinant bacterium or recombinant cell line or recombinant virus, which comprises the recombinant expression vector. The invention also provides application of the antibacterial peptide mutant in preparing any one of antibacterial products, animal feed additives and cosmetic additives. Further, the antibacterial product is any one of antibacterial daily necessities and antibacterial drugs. The antibacterial daily necessities comprise any one of a hand washing liquid and a disinfectant. Further, the antibacterial drug is administered by any one of intravenous injection, oral administration and topical administration. Further, the antibacterial drug also comprises pharmaceutically acceptable auxiliary materials. Further, the auxiliary material is any one of water infusion, powder, lotion, tincture, oil, emulsion, ointment, plaster or aerosol. In summary, compared with t