A bismuth-coordinated bicyclic antibacterial polypeptide, and preparation method and application thereof
Patent Information
- Application Number
- CN202611400942.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-09-10
- Publication Date
- 2026-11-03
AI Technical Summary
Traditional antimicrobial peptides have poor structural stability, short half-life, and safety concerns hinder their large-scale clinical application. Furthermore, long-term use can lead to drug resistance.
The bicyclic antimicrobial peptide with bismuth coordination enhances the structural rigidity and stability of the peptide by introducing cysteine residues on the peptide backbone to coordinate with metal bismuth ions to form a bicyclic structure.
It significantly improved the serum stability and antibacterial activity of the peptide, prolonged its half-life, enhanced its bactericidal effect on bacteria, and reduced the risk of drug resistance.
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Figure CN123026682A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedicine, and in particular to a bismuth-coordinated bicyclic antibacterial polypeptide, its preparation method, and its application. Background Technology
[0002] In the prevention and treatment of microbial infectious diseases, traditional antibiotics, due to their antibacterial activity, have been widely used in clinical medicine, animal husbandry, and food preservation, becoming a core means of controlling infections caused by pathogens such as bacteria and fungi. However, with the long-term and irregular use of traditional antibiotics, their inherent technical defects have become increasingly prominent. Long-term use leading to drug resistance and significant toxic side effects are all challenges that urgently need to be addressed.
[0003] Antimicrobial peptides, as a new type of antimicrobial active substance, have gradually become a research hotspot in this field. Compared with traditional antibiotics, antimicrobial peptides have the following significant advantages: (1) They have a unique mechanism of action, which is to destroy the bacterial cell membrane without a fixed single target, making it difficult for bacteria to develop drug resistance; (2) They have a very broad antimicrobial spectrum, which can kill Gram-positive bacteria, Gram-negative bacteria, fungi, viruses, and parasites at the same time, and are also effective against multidrug-resistant bacteria and superbugs; (3) They have a fast bactericidal speed, which can penetrate and lyse the bacterial cell membrane within minutes, directly achieving the bactericidal effect.
[0004] However, traditional antimicrobial peptides are mostly linear structures with poor structural stability. They are easily affected by various hydrolytic enzymes in the body, resulting in extremely short half-lives. In addition, their safety is also a major obstacle restricting the large-scale clinical application of antimicrobial peptides. Summary of the Invention
[0005] The main objective of this invention is to provide a bismuth-coordinated bicyclic antibacterial polypeptide, its preparation method, and its application, which enhances the antibacterial effect while improving the stability of the polypeptide.
[0006] To achieve the above objectives, the present invention provides a bismuth-coordinated bicyclic antibacterial polypeptide, wherein the bismuth-coordinated bicyclic antibacterial polypeptide is a bicyclic polypeptide formed by using an antibacterial polypeptide containing three cysteine residues as the polypeptide backbone and metallic bismuth as a cyclized linker, and by the linker coordinating with the three cysteine residues on the polypeptide backbone. The amino acid sequence of the polypeptide backbone is Y. (m) CX (n) CX (n) CY (m) , where m = 0 or 1, n = 3 or 4, C represents cysteine (Cys), each X is independently selected from hydrophobic amino acids or positively charged amino acids, and each Y is independently selected from positively charged amino acids.
[0007] In this invention, hydrophobic amino acids include, but are not limited to, phenylalanine (Phe), tryptophan (Trp), leucine (Leu), and isoleucine (Ile); positively charged amino acids include, but are not limited to, arginine (Arg), lysine (Lys), and histidine (His).
[0008] Furthermore, the amino acid sequence of the polypeptide backbone is mirror-symmetrical with the central C as the symmetry point.
[0009] Further, the amino acid sequence of the polypeptide backbone is any one of KCKWLRCRLWKCK, CRWWCWRRC, CWWRCWRRC, CWWWCRRRC, CWRWRCRWRWC, CRRWWCWWRRC, CRWWRCRWWRC, CWWRWCRRWRC, CWWWWCRRRRC, KCRWWRCRWWRCK, RCRWWRCRWWRCR, and KCKRLWCWLRKCK.
[0010] Furthermore, the structural formula of the bismuth-coordinated bicyclic antimicrobial polypeptide is shown in any one of Formulas 1 to 12:
[0011] Formula 1
[0012] Formula 2
[0013] Formula 3
[0014] Formula 4
[0015] Formula 5
[0016] Formula 6
[0017] Formula 7
[0018] Formula 8
[0019] Formula 9
[0020] Formula 10
[0021] Formula 11
[0022] Equation 12.
[0023] This invention also provides a method for preparing the above-mentioned bismuth-coordinated bicyclic antibacterial polypeptide, comprising the following steps: S1: The polypeptide backbone was synthesized using the Fmoc solid-phase synthesis method, and the amino terminus of the polypeptide backbone was blocked using acetic anhydride and pyridine. S2: Dissolve the amino-terminated polypeptide backbone and adjust the pH, then add TCEP first, followed by the addition of bismuth metal salt. After the reaction, the bismuth-coordinated bicyclic antibacterial polypeptide is obtained.
[0024] Furthermore, the metallic bismuth salt is selected from any one of bismuth trichloride, bismuth tribromide, bismuth nitrate, and bismuth acetate.
[0025] The present invention also provides the application of the above-mentioned bismuth-coordinated bicyclic antibacterial polypeptide in the preparation of a drug for treating bacterial infections.
[0026] The present invention also provides a bacterial infection treatment drug comprising the above-mentioned bismuth-coordinated bicyclic antibacterial polypeptide.
[0027] Furthermore, the drug is an injection, a topical application, or an ointment.
[0028] The beneficial effects of this invention are reflected in: The polypeptide backbone comprises a positively charged amino acid region, a hydrophobic amino acid region, and three cysteine residues located at different sites (e.g., CRWWCWRRC and KCKWLRCRLWKCK, where the cysteine residues (C) are located at positions (i, i+4, i+8; i, i+5, i+10) on the polypeptide backbone, respectively). The polypeptide backbone coordinates with bismuth ions through the side chain thiol groups of the aforementioned cysteine residues to form a bicyclic polypeptide. This invention utilizes bismuth metal to cyclize antibacterial polypeptides, improving the structural rigidity of the polypeptide and significantly reducing the probability of hydrolysis by proteases in serum, thereby resulting in a longer half-life.
[0029] Antimicrobial peptides can inhibit bacterial proliferation, and metallic bismuth itself also has antibacterial activity. For example, bismuth potassium citrate in the quadruple therapy for Helicobacter pylori can significantly improve the serum stability of antimicrobial peptides and enhance their antimicrobial activity after combining metallic bismuth with antimicrobial peptides, thus exhibiting better antimicrobial effects and having broad application prospects.
[0030] The bismuth-coordinated bicyclic antibacterial polypeptide of the present invention was verified to have improved structural stability after cyclization through serum stability and glutathione stability tests. Its bactericidal effect was verified through bacterial sterilization and bacterial live-dead staining experiments.
[0031] The preparation process of the bismuth-coordinated bicyclic antimicrobial peptide of the present invention is simple and efficient. It only requires the introduction of cysteine at the (i, i+4, i+8; i, i+5, i+10) position of the antimicrobial peptide and the coordination of the metal bismuth ion with the thiol group of cysteine to obtain the peptide. Attached Figure Description
[0032] Figure 1 High-performance liquid chromatography retention time chromatogram of bismuth-coordinated bicyclic antibacterial peptide Bi-KCKWLRCRLWKCK.
[0033] Figure 2 Mass spectrum of the bismuth-coordinated bicyclic antibacterial peptide Bi-KCKWLRCRLWKCK.
[0034] Figures 3 to 13 The images show, in order, the structural formulas, high-performance liquid chromatography retention time chromatograms, and mass spectra of the bismuth-coordinated bicyclic antibacterial peptides obtained in Examples 2-12.
[0035] Figure 14 A comparison of the stability of the bismuth-coordinated bicyclic antibacterial peptide Bi-KCKWLRCRLWKCK and the linear peptide KCKWLRCRLWKCK in serum.
[0036] Figure 15 Stability of the bismuth-coordinated bicyclic antimicrobial peptide Bi-KCKWLRCRLWKCK at high concentrations of reduced glutathione.
[0037] Figure 16 The bactericidal kinetics curves of the bismuth-coordinated bicyclic antimicrobial peptide Bi-KCKWLRCRLWKCK are shown, with the left graph showing its effect against Staphylococcus aureus and the right graph showing its effect against Escherichia coli.
[0038] Figure 17 The images show the live and dead staining of bacteria by the bismuth-coordinated bicyclic antimicrobial peptide Bi-KCKWLRCRLWKCK. The top image shows the live and dead staining of Staphylococcus aureus, and the bottom image shows the live and dead staining of Escherichia coli. Red fluorescence represents dead bacteria, and green fluorescence represents live bacteria. Detailed Implementation
[0039] To enable those skilled in the art to more clearly understand the technical solutions described in this invention, the following embodiments are provided for illustration. It should be noted that the following embodiments do not constitute a limitation on the scope of protection claimed by this invention.
[0040] Unless otherwise specified, the raw materials, reagents or devices used in the following embodiments can be obtained from conventional commercial sources or by existing known methods; unless otherwise specified, the methods used in the embodiments of the present invention are methods mastered by those skilled in the art.
[0041] Example 1 Preparation of bismuth-coordinated bicyclic antimicrobial peptides The bismuth-coordinated bicyclic antibacterial polypeptide sequence prepared in this embodiment is represented as Bi-KCKWLRCRLWKCK, and its specific structural formula is as follows:
[0042] Its cyclization center, formed by coordination of bismuth metal and three cysteine residues at different positions of an antimicrobial polypeptide (amino acid sequence KCKWLRCRLWKCK), is shown in the following formula:
[0043] The synthetic route of the bismuth-coordinated bicyclic antibacterial peptide in this embodiment is as follows:
[0044] The specific synthesis method is as follows: S1: The linear polypeptide KCKWLRCRLWKCK was synthesized based on the Fmoc solid-phase synthesis method.
[0045] Solid-phase synthesis (SPPS) was employed. First, 200 mg of Rink Amide-MBHA resin was weighed and swollen in DMF for 30 min. Then, a deprotection solution (piperazine: DBU: DMF = 2.5: 1: 50, g / v / v) was added and the mixture was deprotected under nitrogen atmosphere for 8 min. This process was repeated twice. After deprotection, the resin was washed three times with DMF and DCM, respectively. Next, 5 eq of amino acids (all amino acids were protected with both Fmoc and side chains) and 4.9 eq of HATU were weighed and dissolved thoroughly in DMF. Then, 10 eq of DIPEA was added to adjust the alkalinity and activate the amino acids. The mixture was then transferred to the resin and reacted for 1 hour. This process was repeated twice. After completion, the excess reaction solution was removed by washing three times with DMF and DCM alternately. The deprotection, washing, and amino acid addition reaction steps were repeated until the last amino acid was obtained and the polypeptide sequence KCKWLRCRLWKCK was obtained. The Fmoc protection was removed and the polypeptide was washed. 10 mL of amino-terminal blocking solution (pyridine: acetic anhydride: DMF = 1:1:8, v / v / v) was added and the reaction was carried out for 10 min. The operation was repeated twice. After washing three times with DMF and DCM alternately, the resin was washed with methanol and dried with nitrogen.
[0046] Weigh 100 mg of dried resin and add 2 mL of peptide cleavage buffer (TFA: H2O: TIS = 95%: 2.5%: 2.5%). Shake the mixture on a shaker for two hours to cleave the peptide from the resin. Dry the cleavage buffer with dry nitrogen gas. Add 10 mL of ice-cold ether to precipitate the peptide and centrifuge at 5000 rpm for 5 min. Discard the supernatant and dry the ether with dry nitrogen gas. Finally, add 4 mL of water and acetonitrile (H2O:ACN = 1:1, v / v) to dissolve and filter to remove the resin. After freeze-drying, obtain the crude linear peptide product.
[0047] S2: Synthesis of Bi-KCKWLRCRLWKCK based on liquid-phase cyclization In a 100 mL glass flask, 50 mg of the crude linear polypeptide was dissolved in 20 mL of H2O and 5 mL of DMSO. The pH was adjusted to 7.5 using an alkaline Tris-HCl buffer solution, and the stirring speed was controlled at 300 rpm. 2.5 eq TCEP was added to prevent side reactions, followed by 1.2 eq BiBr3. After reacting for 6 h, a pale yellow emulsion was observed, indicating successful cyclization and the cyclized polypeptide was obtained.
[0048] S3: Post-processing of cyclized peptides The cyclized peptide was centrifuged (5000 rpm) to remove the precipitate, and then dialyzed in 2 L of ultrapure water using a dialysis bag with a molecular weight cutoff of 500 Da to remove excess salt ions and DMSO solvent. The water was changed 3 times during dialysis, each time for 4 hours. After dialysis, the solvent was removed by freeze drying to obtain a dry powder product. After purification by high performance liquid chromatography (HPLC), it was freeze dried again to obtain the target product, the bismuth-coordinated bicyclic antibacterial peptide Bi-KCKWLRCRLWKCK.
[0049] To characterize the structure of the material, 1 mg of Bi-KCKWLRCRLWKCK lyophilized powder was added to 1 mL of deionized water, dissolved by sonication, and filtered through a polytetrafluoroethylene filter to obtain a high-performance liquid chromatography (HPLC) sample for purity analysis. The HPLC conditions were as follows: column type Poroshell 120 EC-C18 column, 4.6 × 150 mm; mobile phase A: ultrapure water (0.1% TFA); B: ACN; flow rate 1 mL / min; acetonitrile ratio 10% ACN - 90% ACN; injection volume 20 - 50 μL; detection wavelength 220 nm.
[0050] Figure 1The HPLC retention time chromatogram of Bi-KCKWLRCRLWKCK shows that the retention time of Bi-KCKWLRCRLWKCK is 8.428 min, and the purity of the sample is 99.21% according to HPLC analysis.
[0051] The purified Bi-KCKWLRCRLWKCK sample was further analyzed by mass spectrometry, and the chemical formula of the molecule was analyzed using ChemDraw software. 81 H 131 BiN 26 O 14 S3 has a molecular weight of 1997.9 Da and a theoretical mass-to-charge ratio of 1998.9 / 999.6 / 666.9 / 500.5 / 400.5 / 333.9. Figure 2 As shown in the Bi-KCKWLRCRLWKCK mass spectrum, mass spectrometry analysis revealed that the actual mass-to-charge ratio of the molecules in this segment is 999.5 / 666.9 / 500.5 / 400.6. The appearance of four multiply charged molecular ion peaks proves that the material was successfully synthesized.
[0052] Example 2-12 Preparation of bismuth-coordinated bicyclic antimicrobial peptides The sequence representations of the bismuth-coordinated bicyclic antibacterial peptides prepared in Examples 2-12 are as follows: Example 2: Bi-CRWWCWRRC; Example 3: Bi-CWWRCWRRC; Example 4: Bi-CWWWCRRRC; Example 5: Bi-CWRWRCRWRWC; Example 6: Bi-CRRWWCWWRRC; Example 7: Bi-CRWWRCRWWRC; Example 8: Bi-CWWRWCRRWRC; Example 9: Bi-CWWWWCRRRRC; Example 10: Bi-KCRWWRCRWWRCK; Example 11: Bi-RCRWWRCRWWRCR; Example 12: Bi-KCKRLWCWLRKCK; The structural formulas are as follows: Figure 3-13 As shown. Their preparation methods are basically the same as in Example 1, except that the linear polypeptide sequences synthesized in step S1 of Examples 2-12 are different, as shown in the polypeptide sequences above.
[0053] The high-performance liquid chromatography retention time chromatograms and mass spectra of the bismuth-coordinated bicyclic antibacterial peptides prepared in Examples 2-12 are also shown below. Figure 3-13 As shown, the successful synthesis of the corresponding structural polypeptides has been confirmed.
[0054] Experimental Example 1 Serum stability assay of bismuth-coordinated bicyclic antimicrobial peptides To verify the stability difference between the bismuth-coordinated bicyclic antibacterial peptide and the original linear peptide, and to verify the stability of the peptide under different serum concentrations, the linear peptide KCKWLRCRLWKCK prepared in Example 1 and the bismuth-coordinated bicyclic antibacterial peptide Bi-KCKWLRCRLWKCK were co-incubated with 25% and 50% serum, respectively. Serum samples were collected at different time points, quenched with ice-cold ether, and centrifuged for 15 min (8000 rpm). The supernatant was then analyzed by high-performance liquid chromatography (HPLC) to determine the remaining peptide content, and the results were plotted. Figure 14 It can be seen that, under different serum concentrations, the stability of bismuth-coordinated bicyclic antibacterial peptides is better than that of linear peptides, and their half-life is increased by about 5 times, proving that the peptides have a significant improvement in anti-protease hydrolysis effect after cyclization.
[0055] Experimental Example 2 Reduction effect experiment of bismuth-coordinated bicyclic antibacterial peptide The cellular environment in the human body contains a large amount of reduced glutathione, which can specifically bind to the sulfhydryl groups in polypeptides, thereby reducing the bismuth-coordinated bicyclic antibacterial polypeptide to a linear polypeptide. To observe whether this effect exists, the bismuth-coordinated bicyclic antibacterial polypeptide Bi-KCKWLRCRLWKCK prepared in Example 1 was mixed with a high dose of glutathione, and its remaining content was detected by high-performance liquid chromatography at different time points. The results are as follows. Figure 15 As shown, Bi-KCKWLRCRLWKCK is generally stable in a 10 mmol / L glutathione environment, but partially degrades over time in a 20 mmol / L glutathione environment, demonstrating that this cyclic structure has good glutathione stability.
[0056] Experimental Example 3 Antibacterial activity assay of bismuth-coordinated bicyclic antimicrobial peptides The antibacterial activity of 12 bismuth-coordinated bicyclic antimicrobial peptides prepared in Examples 1 to 12 was tested. The minimum inhibitory concentration (MIC) is an important indicator for evaluating the antibacterial activity of compounds in vitro; the smaller the MIC value, the stronger the bactericidal effect. This experiment investigated the antimicrobial activity of a series of bismuth-coordinated bicyclic antimicrobial peptides against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (S. aureus). S. aureus ATCC 25923), Escherichia coli ( E. coli ATCC 25922), Acinetobacter baumannii ( A. baumannii ATCC19606) and Pseudomonas aeruginosa ( P. aeruginosa (ATCC27853), with the MIC assays of three antibiotics used as controls. The results are shown in Table 1 below: Table 1. Minimum inhibitory concentrations (μM) against 5 bacterial strains
[0057] Table Notes: BiP-1 to BiP-11 represent the bismuth-coordinated bicyclic antibacterial peptides Bi-CRWWCWRRC (Example 2); Bi-CWWRCWRRC (Example 3); Bi-CWWWCRRRC (Example 4); Bi-CWRWRCRWRWC (Example 5); Bi-CRRWWCWWRRC (Example 6); Bi-CRWWRCRWWRC (Example 7); Bi-CWWRWCRRWRC (Example 8); Bi-CWWWWCRRRRC (Example 9); Bi-KCRWWRCRWWRCK (Example 10); Bi-RCRWWRCRWWRCR (Example 11); Bi-KCKRLWCWLRKCK (Example 12). BiP-12 represents the bismuth-coordinated bicyclic antibacterial peptide Bi-KCKWLRCRLWKCK prepared in Example 1; P-12 represents the linear peptide KCKWLRCRLWKCK.
[0058] The results showed that the Bi-KCKWLRCRLWKCK prepared in Example 1 had the best antibacterial activity, while the antibacterial effect of its uncyclized linear polypeptide KCKWLRCRLWKCK was significantly reduced, indicating that the antibacterial effect of the bismuth-coordinated bicyclic antibacterial polypeptide was effectively improved compared with the original linear polypeptide.
[0059] Experiment Example 4 Experiment on the bactericidal effect of bismuth-coordinated bicyclic antibacterial peptides Having already determined the minimum inhibitory concentration (MIC) of the bismuth-coordinated bicyclic antibacterial peptide Bi-KCKWLRCRLWKCK against bacteria in Example 1 (see Experimental Example 3), Gram-positive bacteria were tested. S. aureus With Gram-negative bacteria E. coli As the research subject, bacteria in the logarithmic growth phase were diluted to 1×10⁻⁶ using LB liquid medium. 8 CFU / mL was mixed with the bismuth-coordinated bicyclic antibacterial peptide Bi-KCKWLRCRLWKCK to obtain 4×MIC and 8×MIC mixtures. At multiple time points, equal volumes of the mixture were taken, diluted a certain factor, and spread onto solid LB medium. This was repeated three times in parallel. After incubation at 37℃ for 24 hours, colony counting was performed, and bacterial killing kinetic curves were plotted. Figure 16 The analysis results show that at a concentration of 4×MIC, the cyclic antimicrobial peptide rapidly killed all bacteria within 2 hours, and at a higher concentration of 8×MIC, it killed all pathogenic bacteria in just 1 hour, proving that the bismuth-coordinated bicyclic antimicrobial peptide has excellent bactericidal efficiency.
[0060] Experimental Example 5 Bacterial live / dead staining assay of bismuth-coordinated bicyclic antimicrobial peptides To further observe the bactericidal effect of bismuth-coordinated bicyclic antibacterial peptides, an investigation was designed to examine their activity against Gram-positive bacteria. S. aureus With Gram-negative bacteria E. coli The destructive effect. Take 1×10 8 CFU / mL bacterial suspensions were mixed with equal volumes of the bismuth-coordinated bicyclic antibacterial peptide Bi-KCKWLRCRLWKCK from Example 1 at 4×MIC and 8×MIC, respectively. After half an hour, the mixtures were centrifuged to obtain bacterial pellets, which were then incubated with DMAO / PI dye in the dark for half an hour. The pellets were then photographed using a fluorescence microscope. Figure 17 Image analysis revealed that after incubation with high-concentration antimicrobial peptides for only half an hour, most bacteria were killed, with only a small amount of green fluorescence remaining. Figure 16 The results are consistent with the bactericidal kinetic curves, proving that the cyclic antimicrobial peptides have excellent antibacterial effects.
[0061] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A bismuth-coordinated bicyclic antibacterial polypeptide, characterized in that, The bismuth-coordinated bicyclic antibacterial polypeptide is a bicyclic polypeptide formed by using an antibacterial polypeptide containing three cysteine residues as the polypeptide backbone and metallic bismuth as a cyclized linker, through which the linker coordinates with the three cysteine residues on the polypeptide backbone. The amino acid sequence of the polypeptide backbone is Y. (m) CX (n) CX (n) CY (m) , where m = 0 or 1, n = 3 or 4, C represents cysteine, each X is independently selected from hydrophobic amino acids or positively charged amino acids, and each Y is independently selected from positively charged amino acids.
2. The bismuth-coordinated bicyclic antibacterial polypeptide as described in claim 1, characterized in that, The amino acid sequence of the polypeptide backbone is mirror-symmetrical with the C in the middle as the symmetry point.
3. The bismuth-coordinated bicyclic antibacterial polypeptide as described in claim 1, characterized in that, The amino acid sequence of the polypeptide backbone is any one of KCKWLRCRLWKCK, CRWWCWRRC, CWWRCWRRC, CWWWCRRRC, CWRWRCRWRWC, CRRWWCWWRRC, CRWWRCRWWRC, CWWRWCRRWRC, CWWWWCRRRRC, KCRWWRCRWWRCK, RCRWWRCRWWRCR, and KCKRLWCWLRKCK.
4. The bismuth-coordinated bicyclic antibacterial polypeptide as described in claim 1, characterized in that, The structural formula of the bismuth-coordinated bicyclic antimicrobial peptide is shown in any one of Formulas 1 to 12: Formula 1 Formula 2 Formula 3 Formula 4 Formula 5 Formula 6 Formula 7 Formula 8 Formula 9 Formula 10 Formula 11 Equation 12.
5. The method for preparing the bismuth-coordinated bicyclic antibacterial polypeptide according to any one of claims 1 to 4, characterized in that, Includes the following steps: S1: The polypeptide backbone was synthesized using the Fmoc solid-phase synthesis method, and the amino terminus of the polypeptide backbone was blocked using acetic anhydride and pyridine. S2: Dissolve the amino-terminated polypeptide backbone and adjust the pH, then add TCEP first, followed by the addition of bismuth metal salt. After the reaction, the bismuth-coordinated bicyclic antibacterial polypeptide is obtained.
6. The method for preparing the bismuth-coordinated bicyclic antibacterial polypeptide as described in claim 5, characterized in that, The metallic bismuth salt is selected from any one of bismuth trichloride, bismuth tribromide, bismuth nitrate, and bismuth acetate.
7. The use of the bismuth-coordinated bicyclic antimicrobial polypeptide as described in any one of claims 1 to 4 in the preparation of a medicament for treating bacterial infections.
8. A bacterial infection treatment drug, characterized in that, A bicyclic antimicrobial polypeptide containing bismuth coordination as described in any one of claims 1 to 4.
9. The bacterial infection treatment drug as described in claim 8, characterized in that, The drug is an injection, a topical liniment, or an ointment.