Polyamino acid as well as preparation method and application thereof

Abstract

The invention discloses polyamino acid as well as a preparation method and application thereof, and belongs to the technical field of antibacterial polyamino acid. The structure of the polyamino acid is shown as a formula (I). Wherein 10 < = n < = 100, and 2 < = m < = 10; r1 is selected from # imgabs0, R2 is selected from phenyl or methyl, and x is selected from an integer between 1 and 6. The polyamino acid overcomes the limitation problems that the salt sensitivity of natural antibacterial peptide in a complex physiological environment and the activity of the natural antibacterial peptide in a multivalent cation environment is reduced through the combined action of guanidination, the polymerization degree and a side chain length regulation strategy; the antibacterial activity and stability of the polyamino acid in a complex environment are remarkably improved, so that the polyamino acid has excellent broad-spectrum antibacterial property, biocompatibility, degradability and long-acting and stable antibacterial property. # imgabs 1 # formula (I)

Description

Technical Field

[0001] The present invention relates to the technical field of antibacterial polyamino acid, and in particular to a polyamino acid and a preparation method and application thereof. Background Art

[0002] In recent years, antimicrobial polyamino acids that mimic the structural features of antimicrobial peptides (such as positive charge and hydrophobic structure) have shown great potential in the treatment of multidrug-resistant microbial infections. First, the tunability of polyamino acids enables them to adjust the amino acid sequence and structure as needed, optimize the antimicrobial effect, and improve the targeting of specific pathogenic microorganisms. This designability makes polyamino acids more flexible in diversified applications. Secondly, polyamino acids generally have good stability. Through the synthesis process, more stable and durable peptide chain structures can be designed, which can avoid the problem of natural antimicrobial peptides losing their activity due to easy degradation by proteases. Furthermore, the production cost of polyamino acids is low. Since they can be mass-produced by the active polymerization method of α-amino acid-N-carboxyl cyclic anhydride (NCA) monomers, the cost is more economical than natural antimicrobial peptides and is convenient for commercial application. Polyamino acids can also overcome the problem of poor toxicity selectivity that may be produced by natural peptides by changing their structure, thereby improving the selectivity and safety of target bacteria. In the field of antimicrobial polyamino acid research, most of the existing studies have focused on modifying certain amino acids (such as histidine, lysine, arginine, glutamic acid, etc.) through polymerization to form polymer materials with antimicrobial properties. Due to their cationic or amphiphilic nature, these amino acids can destroy the membrane structure through electrostatic interactions with bacterial membranes and show significant antibacterial activity. For example, the amino groups of lysine and arginine can enhance the binding force with bacterial membranes, thereby effectively inhibiting bacterial growth. However, the stability of these antibacterial polyamino acids is generally poor, and the antibacterial properties of the polymers are easily reduced in high-salt or high-concentration ion environments. Although antibacterial polyamino acids show good antibacterial activity on some specific microorganisms (such as Escherichia coli and Staphylococcus aureus), their broad-spectrum antibacterial ability against a variety of different pathogens is still insufficient, especially for fungi. The effect is relatively limited.

[0003] Although some research has achieved certain results, there are relatively few studies on antibacterial polyamino acid materials with aspartic acid as the skeleton. Aspartic acid has the characteristics of negatively charged amino acids and its application in antibacterial polymers is relatively limited. Therefore, how to effectively use aspartic acid as the skeleton to design new antibacterial polyamino acid materials and overcome its possible performance limitations is still a key issue in current research. Unlike common antibacterial polyamino acid precursors such as polyglutamic acid benzyl ester, polyaspartic acid benzyl ester can effectively avoid the problem of main chain breakage during the aminolysis modification process. Polyglutamic acid benzyl ester often breaks the polymer main chain during the aminolysis modification process, affecting the structural stability of the polymer. However, polyaspartic acid benzyl ester can achieve quantitative modification during the modification process, and its main chain is not easy to break, maintaining good structural stability. In addition, aspartic acid residues can undergo structural transformation during the aminolysis process, introducing different configurations and sequences into the polymer main chain. Through the advantages of this quantitative modification and structural transformation, polyaspartic acid benzyl ester, as a precursor of antibacterial polymers, can not only maintain structural stability, but also optimize antibacterial properties, opening up a new direction for the design and application of antibacterial polyamino acids.

[0004] Existing antibacterial materials are mainly prepared by guanidinization modification of polylysine, polyornithine, and polyarginine, which leads to a single molecular structure and limits the possibility of further optimizing performance. At the same time, the preparation process of these materials is complicated, the yield is low, and the side chain modification of polyamino acids is difficult, which is not conducive to cost control and large-scale production. The most critical thing is that although these materials have certain antibacterial effects, their antibacterial properties are still limited, especially for broad-spectrum pathogens (Gram-negative bacteria, Gram-positive bacteria, fungi). The effect is not ideal, resulting in a limited scope of practical application. For example, the minimum inhibitory concentration (MIC) for Candida albicans is generally greater than 20 μg / mL, and it has high toxicity to normal cells, resulting in a low selectivity index (SI) of antibacterial polyamino acids, making it difficult to achieve a balance between safety and antibacterial performance. In addition, their antibacterial performance in high-salt environments often decreases significantly, and the lack of salt-sensitive design limits their stability under complex physiological conditions.

[0005] Therefore, it is of great significance to research and develop a new type of antibacterial polyamino acid material with broad-spectrum antibacterial activity, low toxicity, and high salt stability. Summary of the invention

[0006] In view of this, the technical problem to be solved by the present invention is to provide a polyamino acid and a preparation method and application thereof. The polyamino acid has excellent broad-spectrum antibacterial ability, long-term stable antibacterial performance, and good biocompatibility.

[0007] In order to achieve the above purpose, the technical solution adopted by the present invention is as follows: The present invention provides a polyamino acid, the structure of which is shown in formula (I):

[0008] Formula (I); Among them, 10≤n≤100, 2≤m≤10; R1 is selected from , R2 is selected from phenyl or methyl, and x is selected from an integer between 1-6.

[0009] The oblique lines on the main chain in the structure of formula (I) represent two different sequence arrangements of aspartic acid residues in the polyamino acid main chain, and the wavy line in R1 represents the connection position.

[0010] The guanidine group in the polyamino acid of the present invention provides it with strong hydrogen bond donor-acceptor capability and multi-point interaction, thereby ensuring the stability of the antibacterial performance of the polyamino acid. At the same time, the molecular structure is optimized by regulating the degree of polymerization and side chain length of the polyamino acid, thereby improving the salt resistance of the polyamino acid.

[0011] The polyamino acid described in the present invention has excellent antibacterial activity and high selectivity against Gram-positive bacteria - Staphylococcus aureus (S. aureus), Gram-negative bacteria - Escherichia coli (E. coli) and fungi - Candida albicans (C. albicans), and can destroy the integrity of bacterial and fungal cell membranes through physical interaction, showing the characteristics of rapid killing of bacteria and fungi.

[0012] Moreover, the polyamino acid can inhibit the survival rate of fungi to less than 5% within 5 minutes at a concentration of 2×MIC. In a salt environment, the minimum inhibitory concentration (MIC) of the polyamino acid (guanidinized polyamino acid) of the present invention on bacteria is only slightly increased compared to that of the monoamine polyamino acid.

[0013] Preferably, the n is selected from 10, 20, 40 or 100; Preferably, m is selected from 2, 4, 6, 8 or 10; Preferably, x is selected from 1, 4, 5 or 6.

[0014] More preferably, the polyamino acid is selected from any of the following structures: .

[0015] The present invention also provides a method for preparing the above-mentioned polyamino acid, comprising the following steps: (1) The poly(β-benzyl aspartic acid) represented by formula (II) and the diamine compound represented by formula (III) are mixed with a solvent to react to obtain a monoamine polyamino acid represented by formula (IV); (2) reacting a monoamine polyamino acid and 1H-pyrazole-1-carboxamidine hydrochloride under the catalysis of N, N-diisopropylethylamine to obtain a polyamino acid represented by formula (I);

[0016] Formula (II);

[0017] Formula (III);

[0018] Formula (IV); Wherein, y is selected from an integer between 2-10.

[0019] Preferably, in the step (1), the molar ratio of the side chain benzyl group of the poly(β-benzyl aspartic acid) to the diamine compound is 1:(10-50); more preferably 1:(10-40). In some specific embodiments of the present invention, it is preferably 1:20.

[0020] Preferably, the solvent in step (1) is selected from one or more of N-methylpyrrolidone, dimethyl sulfoxide, and N,N-dimethylformamide.

[0021] The present invention has no particular limitation on the amount of the solvent used, as long as it can dissolve the poly(β-benzyl aspartic acid) and the diamine compound.

[0022] Preferably, the reaction temperature in step (1) is 20°C-50°C; more preferably 20°C-40°C. In some specific embodiments of the present invention, the reaction temperature is 25°C.

[0023] Preferably, the reaction time is 1-6 h; more preferably 2-4 h.

[0024] After the reaction in step (1) is completed, post-treatments such as dialysis and freeze-drying are also included.

[0025] Preferably, in the step (2), the mass ratio of the monoamino polyamino acid to 1H-pyrazole-1-carboxamidine hydrochloride is 1:(1-2). In some specific embodiments of the present invention, the mass ratio is preferably 1:2.

[0026] Preferably, the mass ratio of monoamino polyamino acid to N, N-diisopropylethylamine in step (2) is 1:(2-4). In some specific embodiments of the present invention, it is preferably 1:2. Preferably, the solvent for the reaction in step (2) is selected from a mixed solution of methanol and water; The volume of the mixed solution is preferably 0.1-3 mL.

[0027] The volume ratio of methanol to water in the mixed solution is (1-4):1.

[0028] Preferably, the reaction temperature in step (2) is 40°C-65°C, more preferably 50°C-60°C. In some specific embodiments of the present invention, it is preferably 55°C.

[0029] Preferably, the reaction time in step (2) is 20-30 h; more preferably 22-26 h.

[0030] After the reaction in step (2) is completed, post-treatments such as sedimentation and drying are also included.

[0031] The solvent selected for the precipitation is acetone.

[0032] The drying is preferably freeze-drying.

[0033] Preferably, the poly (β-benzyl aspartic acid) is prepared by ring-opening polymerization of β-benzyl aspartic acid-N-carboxyl cyclic anhydride under the action of an initiator; Preferably, the initiator is selected from , R2 is selected from phenyl or methyl, x is selected from an integer between 1 and 6; more preferably, the initiator is selected from C6H5CH2NH2 or CH3(CH2)4NH2 or CH3(CH2)5NH2 or CH3(CH2)6NH2.

[0034] The above-mentioned initiator can be a common commercially available product.

[0035] The temperature of the ring-opening polymerization is preferably 20°C-40°C; more preferably 20°C-30°C.

[0036] The time of the ring-opening polymerization is preferably 2-5 days; more preferably 3-5 days.

[0037] The solvent for the ring-opening polymerization includes, but is not limited to, anhydrous tetrahydrofuran, anhydrous N,N-dimethylformamide, anhydrous dichloromethane, and the like.

[0038] The ratio of the total mass of the β-benzyl aspartic acid-N-carboxyl cyclic anhydride and the initiator to the solvent of the ring-opening polymerization is preferably (2-30) g: (50-200) mL. In some specific embodiments of the present invention, it is preferably 2.86 g: 50 mL or 5.72 g: 50 mL or 11.44 g: 100 mL or 28.59 g: 200 mL.

[0039] The molar ratio of the initiator to the β-benzyl aspartic acid-N-carboxyl cyclic anhydride is 1:(10-100).

[0040] After the ring-opening polymerization is completed, post-treatments such as dialysis and freeze-drying are also included.

[0041] The present invention has no particular limitation on all the above-mentioned post-treatments such as dialysis and freeze-drying, and any method well known to those skilled in the art may be used.

[0042] The present invention also provides the use of the polyamino acid and the polyamino acid prepared by the preparation method in the preparation of antibacterial drugs.

[0043] The polyamino acid described in the present invention is an antibacterial polyamino acid material with a hydrophobic chain as the end group and a guanidine group as the side chain cationic group, which successfully achieves a highly efficient killing effect on targeted bacterial and fungal cell membranes.

[0044] Since the polyamino acid contains an alkaline amino group in the side chain, it is protonated under physiological conditions (neutral or weakly acidic pH) with a large amount of positive charge (called cationic polyamino acid), and can quickly bind to the negatively charged bacterial cell membrane, eventually leading to bacterial death, showing rapid bactericidal kinetics. In addition, the polyamino acid has good biocompatibility. Therefore, the polyamino acid shows good application prospects in antibacterial drugs.

[0045] Compared with the prior art, the polyamino acid provided by the present invention has a structure as shown in formula (I). Wherein, 10≤n≤100, 2≤m≤10; R1 is selected from , R2 is selected from phenyl or methyl, and x is selected from an integer between 1 and 6. The polyamino acid overcomes the limitations of the natural antimicrobial peptides in terms of salt sensitivity in complex physiological environments and decreased activity in multivalent cation environments through the combined action of guanidinization, polymerization degree, and side chain length regulation, and significantly improves the antimicrobial activity and stability of the polyamino acid in complex environments, so that the polyamino acid has excellent broad-spectrum antimicrobial properties, biocompatibility, degradability, and long-term stable antimicrobial properties. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of the poly(β-benzyl aspartic acid) prepared in Example 7; Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of the monoamino polyamino acid prepared in Example 35; Figure 3 is the hydrogen nuclear magnetic resonance spectrum of the polyamino acid prepared in Example 35; Figure 4 This is a graph showing the inhibitory effects of the polyamino acid prepared in Example 35 on Staphylococcus aureus, Escherichia coli, and Candida albicans at different concentrations; Figure 5 These are scanning electron micrographs of Staphylococcus aureus, Escherichia coli, and Candida albicans after being treated with PBS or the cationic polyamino acid prepared in Example 35; Figure 6 This is a graph showing the bactericidal kinetics of the polyamino acid prepared in Example 35 against Candida albicans. DETAILED DESCRIPTION

[0047] In order to further illustrate the present invention, the polyamino acid provided by the present invention and its preparation method and application are described in detail below in conjunction with embodiments.

[0048] The source of the following β-benzyl aspartic acid-N-carboxyl cyclic anhydride is not particularly limited and can be synthesized by referring to the method described in the document published by BA Shidlovsky et al., BA Shidlovsky et al., Al, J. Med. Chem. 1967, 10, 904-908.

[0049] The sources of the following diamine compounds are not particularly limited and can be commercially available.

[0050] The standard strains of Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) were purchased from Shandong Lu Microbiological Technology Co., Ltd.

[0051] The Candida albicans (ATCC 10231) was purchased from Qingdao Haibo Biotechnology Co., Ltd.

[0052] Example 1 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=10: Weigh 0.10 g (1.15 mmol) of n-pentylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 2.86 g (11.47 mmol) of the compound β-benzyl aspartic acid-N-carboxyl ring anhydride dissolved in 50 mL of anhydrous DMF. After stirring and reacting for 72 h at 25°C, dialyze and freeze-dry to obtain a white powder product n-pentylamine-poly (β-benzyl aspartic acid).

[0053]

[0054] Example 2 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=20: Weigh 0.10 g (1.15 mmol) of n-pentylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 5.72 g (22.94 mmol) of the compound β-benzyl aspartic acid-N-carboxyl ring anhydride dissolved in 50 mL of anhydrous DCM. After stirring and reacting at 25°C for 72 h, dialyze and freeze-dry to obtain a white powder product n-pentylamine-poly (β-benzyl aspartic acid).

[0055]

[0056] Example 3 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=40: Weigh 0.10 g (1.15 mmol) of n-pentylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 11.44 g (45.85 mmol) of the compound β-benzyl aspartic acid-N-carboxyl ring anhydride dissolved in 100 mL of anhydrous DCM. After stirring and reacting at 25°C for 72 h, dialyze and freeze-dry to obtain a white powder product n-pentylamine-poly (β-benzyl aspartic acid).

[0057]

[0058] Example 4 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=100: Weigh 0.10 g (1.15 mmol) of n-pentylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 28.59 g (114.72 mmol) of the compound β-benzyl aspartic acid-N-carboxyl ring anhydride dissolved in 200 mL of anhydrous DCM. After stirring and reacting at 25°C for 72 h, dialyze and freeze-dry to obtain a white powder product n-pentylamine-poly (β-benzyl aspartic acid).

[0059]

[0060] Example 5 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=10: Weigh 0.10 g (0.99 mmol) of n-hexylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 2.46 g (9.88 mmol) of the compound β-benzyl aspartic acid-N-carboxyl cyclic anhydride dissolved in 50 mL of anhydrous DMF. After stirring and reacting at 25°C for 72 h, dialyze and freeze-dry to obtain a white powder product n-hexylamine-poly (β-benzyl aspartic acid).

[0061]

[0062] Example 6 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=20: Weigh 0.10 g (0.99 mmol) of n-hexylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 4.93 g (19.76 mmol) of the compound β-benzyl aspartic acid-N-carboxyl cyclic anhydride dissolved in 50 mL of anhydrous DCM. After stirring and reacting at 25°C for 72 h, dialyze and freeze-dry to obtain a white powder product n-hexylamine-poly (β-benzyl aspartic acid).

[0063]

[0064] Example 7 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=40: Weigh 0.10 g (0.99 mmol) of n-hexylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 9.85 g (39.53 mmol) of the compound β-benzyl aspartic acid-N-carboxyl cyclic anhydride dissolved in 100 mL of anhydrous DCM. After stirring and reacting at 25°C for 72 h, dialyze and freeze-dry to obtain a white powder product n-hexylamine-poly (β-benzyl aspartic acid).

[0065]

[0066] Example 8 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=100: Weigh 0.10 g (0.99 mmol) of n-hexylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 24.63 g (98.82 mmol) of the compound β-benzyl aspartic acid-N-carboxyl cyclic anhydride dissolved in 100 mL of anhydrous DCM. After stirring and reacting at 25°C for 72 h, dialyze and freeze-dry to obtain a white powder product n-hexylamine-poly (β-benzyl aspartic acid).

[0067]

[0068] Example 9 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=10: Weigh 0.10 g (0.87 mmol) of n-heptylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 2.16 g (8.68 mmol) of the compound β-benzyl aspartic acid-N-carboxyl ring anhydride dissolved in 50 mL of anhydrous DMF. After stirring and reacting for 72 h at 25°C, dialyze and freeze-dry to obtain a white powder product n-heptylamine-poly (β-benzyl aspartic acid).

[0069]

[0070] Example 10 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=20: Weigh 0.10 g (0.87 mmol) of n-heptylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 4.33 g (17.36 mmol) of the compound β-benzyl aspartic acid-N-carboxyl ring anhydride dissolved in 50 mL of anhydrous DCM. After stirring and reacting at 25°C for 72 h, dialyze and freeze-dry to obtain a white powder product n-heptylamine-poly (β-benzyl aspartic acid).

[0071]

[0072] Embodiment 11 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=40 in the structure of formula (V): Weigh 0.10 g (0.87 mmol) of n-heptylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 8.65 g (34.72 mmol) of the compound β-benzyl aspartic acid-N-carboxyl ring anhydride dissolved in 100 mL of anhydrous DCM. After stirring and reacting at 25°C for 72 h, dialyze and freeze-dry to obtain a white powder product n-heptylamine-poly (β-benzyl aspartic acid).

[0073]

[0074] Example 12 Synthesis of poly(β-benzyl aspartic acid) having the structure of formula (II), wherein n=100: Weigh 0.10 g (0.87 mmol) of n-heptylamine and dissolve it in 10 mL of anhydrous DMF, then quickly add 21.63 g (86.79 mmol) of the compound β-benzyl aspartic acid-N-carboxyl ring anhydride dissolved in 200 mL of anhydrous DCM. After stirring and reacting at 25°C for 72 h, dialyze and freeze-dry to obtain a white powder product n-heptylamine-poly (β-benzyl aspartic acid).

[0075]

[0076] Example 13 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10; Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 1, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0077] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0078]

[0079] Embodiment 14 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 1, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0080] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0081]

[0082] Embodiment 15 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 1, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0083] Weigh 0.10 g (the side groups contain 0.47 mmol of amine groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0084]

[0085] Example 16 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 1, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0086] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0087]

[0088] Embodiment 17 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 1, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0089] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0090]

[0091] Embodiment 18 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 2, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0092] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0093]

[0094] Embodiment 19 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 2, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0095] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0096]

[0097] Embodiment 20 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 2, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0098] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0099]

[0100] Embodiment 21 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 2, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0101] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0102]

[0103] Embodiment 22 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 2, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0104] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0105]

[0106] Embodiment 23 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 3, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0107] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0108]

[0109] Embodiment 24 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 3, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0110] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0111]

[0112] Embodiment 25 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 3, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0113] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0114]

[0115] Embodiment 26 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 3, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0116] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0117]

[0118] Embodiment 27 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 3, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0119] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0120]

[0121] Embodiment 28 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 4, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0122] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0123]

[0124] Embodiment 29 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 4, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0125] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0126]

[0127] Embodiment 30 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 4, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0128] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0129]

[0130] Embodiment 31 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 4, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0131] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0132]

[0133] Embodiment 32 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 4, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0134] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0135]

[0136] Embodiment 33 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 5, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0137] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0138]

[0139] Embodiment 34 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 5, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0140] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0141]

[0142] Embodiment 35 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol of benzyl groups) of the poly (β-benzyl aspartic acid) obtained in Example 5, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0143] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0144]

[0145] Embodiment 36 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 5, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0146] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0147]

[0148] Embodiment 37 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 5, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0149] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0150]

[0151] Embodiment 38 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 6, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0152] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0153]

[0154] Embodiment 39 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 6, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0155] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0156]

[0157] Embodiment 40 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 6, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0158] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0159]

[0160] Embodiment 41 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol of benzyl groups) of the poly (β-benzyl aspartic acid) obtained in Example 6, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0161] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0162]

[0163] Embodiment 42 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 6, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0164] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0165]

[0166] Embodiment 43 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol of benzyl groups) of the poly (β-benzyl aspartic acid) obtained in Example 7, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0167] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0168]

[0169] Embodiment 44 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 7, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0170] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0171]

[0172] Embodiment 45 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 7, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0173] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0174]

[0175] Embodiment 46 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 7, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0176] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0177]

[0178] Embodiment 47 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 7, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0179] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0180]

[0181] Embodiment 48 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 8, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0182] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0183]

[0184] Embodiment 49 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 8, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0185] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0186]

[0187] Embodiment 50 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 8, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0188] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0189]

[0190] Embodiment 51 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 8, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0191] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0192]

[0193] Embodiment 52 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 8, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0194] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0195]

[0196] Embodiment 53 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 9, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0197] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0198]

[0199] Embodiment 54 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 9, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0200] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0201]

[0202] Embodiment 55 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 9, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0203] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0204]

[0205] Embodiment 56 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 9, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0206] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0207]

[0208] Embodiment 57 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=10: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 9, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0209] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0210]

[0211] Embodiment 58 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 10, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0212] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0213]

[0214] Embodiment 59 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 10, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0215] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0216]

[0217] Embodiment 60 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol of benzyl groups) of the poly (β-benzyl aspartic acid) obtained in Example 10, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0218] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0219]

[0220] Embodiment 61 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol of benzyl groups) of the poly (β-benzyl aspartic acid) obtained in Example 10, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0221] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0222]

[0223] Embodiment 62 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=20: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 10, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0224] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0225]

[0226] Embodiment 63 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 11, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0227] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0228]

[0229] Embodiment 64 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 11, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0230] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0231]

[0232] Embodiment 65 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 11, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0233] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0234]

[0235] Embodiment 66 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 11, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0236] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0237]

[0238] Embodiment 67 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=40: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 11, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0239] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0240]

[0241] Embodiment 68 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 12, then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0242] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 hours. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0243]

[0244] Embodiment 69 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 12, then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0245] Weigh 0.10 g (the side groups contain 0.54 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0246]

[0247] Embodiment 70 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 12, then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0248] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0249]

[0250] Embodiment 71 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol of benzyl groups) of the poly (β-benzyl aspartic acid) obtained in Example 12, then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0251] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0252]

[0253] Embodiment 72 Synthesis of guanidinized polyamino acid having the structure of formula (I), wherein n=100: Weigh 0.20 g (the side groups contain 0.98 mmol benzyl groups in total) of the poly (β-benzyl aspartic acid) obtained in Example 12, then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved, seal and react at 25°C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamine polyamino acid represented by formula (IV).

[0254] Weigh 0.10 g (the side groups contain 0.37 mmol of amine groups in total) of the monoamine polyamino acid material having the structure of formula (IV) prepared above, dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboxamidine hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55°C for 24 h. After the reaction stops, use acetone to precipitate and methanol to dissolve, repeat three times, and freeze-dry to obtain a white powder polyamino acid material with the following structure.

[0255]

[0256] Performance test experiment (I) Structural detection of the polyamino acid materials having the structures of formula (I), formula (II) and formula (IV) obtained in the above examples.

[0257] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of the poly(β-benzyl aspartic acid) represented by formula (II) prepared in Example 7.

[0258] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of the monoamino polyamino acid prepared in Example 35. Figure 2 It can be seen that the side group of poly(β-benzyl aspartic acid) is successfully bonded to the monoamine group to obtain a monoamine polyamino acid having the structure of formula (IV).

[0259] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of the guanidinated polyamino acid prepared in Example 35. Figure 3 It can be seen that the side group of the monoamine polyamino acid having the formula (IV) is successfully bonded to the guanidinium group to obtain the guanidinium polyamino acid having the structure of the formula (I).

[0260] (II) Testing the inhibition of different bacteria at different concentrations The results of the inhibition of different bacteria by the guanidinium polyamino acid having the structure of formula (I) prepared in Example 35 at different concentrations are as follows: Figure 4 shown.

[0261] (III) In vitro antibacterial activity test of guanidinated polyamino acids (well plate method) The guanidine-based antibacterial polyamino acid having the structure of formula (I) was co-cultured with Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Candida albicans (ATCC 10231), and the minimum inhibitory concentration (MIC) thereof was detected: First, Staphylococcus aureus and Escherichia coli were inoculated into fresh MH medium and cultured at 37°C for 10 h. The bacteria in the logarithmic phase were diluted with fresh MH medium and the bacteria (100 μL, 1×10 6 CFU / mL) was added to a 96-well plate. The polyamino acid (guanidinium polyamino acid) material of the present invention was diluted by gradient dilution. Then, PBS (pH=7.4) as a control group and the diluted guanidinium polyamino acid material (100 µL) were added to the 96-well plate, shaken for 60 s using a microplate reader to mix them evenly, and the optical density at 600 nm was measured. The culture plate was incubated at 37°C for 24 h, and then the optical density of the microbial solution was measured at 600 nm. MIC is the lowest concentration at which bacterial growth is undetectable. Candida albicans was inoculated in fresh Sabouraud medium and cultured at 30°C for 24 h. The fungus in the logarithmic phase was diluted with fresh RPMI-1640 medium, and the bacteria (100 µL, 1×10 5 CFU / mL) were added into a 96-well plate. The rest of the operation was similar to the above.

[0262] 4. Measuring the stability of MIC of guanidinated polyamino acids in salt environment (anti-salt sensitivity) The method is: add NaCl to the culture medium and adjust the concentration of NaCl to 0.09 g / mL to simulate a high-salt environment, measure the MIC of guanidinized polyamino acids in this environment, and compare it with the MIC in a normal environment (without NaCl). If the MIC in a high-salt environment is similar to or not much different from the MIC in a normal environment, it indicates that the polyamino acid has good salt resistance sensitivity.

[0263] The results of the minimum inhibitory concentration test and salt sensitivity test for different bacteria are shown below: (1) The results of the minimum inhibitory concentration of the guanidinated polyamino acid having the structure of formula (I) prepared in Example 35 against different bacteria are shown in Table 1.

[0264] Table 1 Minimum inhibitory concentration (MIC, µg / mL) of the polyamino acids prepared in Example 35 against different bacteria

[0265] Note: a It means that the measurement was carried out in 0.09 g / mL NaCl, simulating a high-salt environment.

[0266] The results in Table 1 show that the monoamine polyamino acid prepared in Example 35 has a MIC of 7.8 µg / mL for Staphylococcus aureus and a MIC of 7.8 µg / mL for Escherichia coli, but does not have antifungal ability, while the guanidated polyamino acid material prepared in Example 35 has good antibacterial activity against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Candida albicans (ATCC10231), and its MIC is between 3.9 and 7.8 µg / mL, and has a more excellent broad-spectrum antibacterial activity. In addition, in a NaCl environment simulating a high-salt environment, the monoamine polyamino acid prepared in Example 35 has a MIC of 250 µg / mL for Staphylococcus aureus and a MIC of 500 µg / mL for Escherichia coli, which has increased by more than 30 times, while the MIC of the guanidated polyamino acid prepared in Example 35 against the three bacteria is only slightly increased by 1-4 times, indicating that it has salt resistance sensitivity.

[0267] (2) The minimum inhibitory concentration of the guanidinated polyamino acid having the structure of formula (I) prepared in Example 13 against different bacteria is shown in Table 2.

[0268] Table 2 Minimum inhibitory concentration (MIC, µg / mL) of the polyamino acids prepared in Example 13 against different bacteria

[0269] Note: a It means that the measurement was performed in 0.09 g / mL NaCl, simulating a high-salt environment.

[0270] The results in Table 2 show that the monoamine polyamino acid prepared in Example 13 has a MIC of 62.5 µg / mL against Staphylococcus aureus and a MIC of 125 µg / mL against Escherichia coli, which shows weak antibacterial activity and no antifungal ability. The polyamino acid (guanidinized polyamino acid) material prepared in Example 13 has significant antibacterial activity against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Candida albicans (ATCC 10231), and its MIC is between 7.8 and 15.6 µg / mL, indicating that it has broad-spectrum antibacterial activity. In addition, in a NaCl environment simulating a high-salt environment, the monoamine polyamino acid prepared in Example 13 loses its antibacterial activity, and its MIC against bacteria is greater than 500 µg / mL. However, in a high-salt environment, the MIC of the guanidinated polyamino acid prepared in Example 13 increased from 7.8-15.6 µg / mL to 31.2-62.5 µg / mL, and the antibacterial activity decreased slightly, indicating that it has salt sensitivity.

[0271] (3) The results of the minimum inhibitory concentration of the guanidinated polyamino acid having the structure of formula (I) prepared in Example 72 against different bacteria are shown in Table 3.

[0272] Table 3 Minimum inhibitory concentration (MIC, µg / mL) of the antibacterial polyamino acids in Example 72 against different bacteria

[0273] Note: a It means that the measurement was performed in 0.09 g / mL NaCl, simulating a high-salt environment.

[0274] The results in Table 3 show that the monoamine polyamino acid prepared in Example 72 has a MIC of 7.8 μg / mL for Staphylococcus aureus and Escherichia coli in a normal environment or a high-salt environment, and its antibacterial effect on the two bacteria is salt-sensitive, but in a normal environment, it has a weak inhibitory ability against Candida albicans, with a MIC of 125 μg / mL, and its antifungal ability is lost in a high-salt environment. The guanidinated polyamino acid material prepared in Example 72 has significant antibacterial activity against Staphylococcus aureus (ATCC25923), Escherichia coli (ATCC 25922) and Candida albicans (ATCC 10231), and its MIC is between 1.8 and 3.9 μg / mL, and has a broad-spectrum antibacterial activity. In addition, in a high-salt environment, the MIC of the high-polymerization guanidinated polyamino acid prepared in Example 72 does not change for the three bacteria, indicating that it has salt-sensitivity.

[0275] (V) Test on the ability of guanidinium polyamino acids to destroy bacterial cell membranes The morphology of bacterial cell membranes treated with the polyamino acid (guanidinized polyamino acid) material prepared in Example 35 was verified by using a scanning electron microscope to photograph the following: First, Staphylococcus aureus and Escherichia coli were inoculated in fresh MH medium or LB medium and cultured at 37°C for 10 h, washed three times with PBS (pH = 7.4) and resuspended. The final concentration of the bacterial solution was 2×10 6 CFU / mL. 500.0 μL of bacterial suspension and 500.0 μL of 15.6 μg / mL guanidinized polyamino acid solution were mixed evenly, incubated at 37°C for 30 min, centrifuged to collect the treated bacterial samples, and then washed twice with PBS.

[0276] Then, the cells were fixed with 4% paraformaldehyde solution at 25°C for 5 h.

[0277] Subsequently, the samples were washed once with PBS and dehydrated with gradient ethanol solutions (10%, 25%, 50%, 75%, 90% and 100%). Finally, the bacterial samples were dropped on the silicon wafer and the treated bacterial samples were observed by scanning electron microscopy (SEM). For Candida albicans, it was inoculated in fresh Sabouraud medium and cultured at 30°C for 24 h, washed three times with PBS (pH = 7.4) and resuspended. The final concentration of the bacterial solution was 2×10 5 CFU / mL. The rest of the operation is similar to that of bacteria.

[0278] Figure 5 This is the bacterial morphology after treatment with guanidinium polyamino acid in Example 35. Figure 5 The results show that the guanidinated polyamino acid has a good ability to destroy bacterial cell membranes.

[0279] (VI) Bactericidal kinetics test of guanidinium polyamino acids (fungal plate count method) Candida albicans was inoculated in fresh Sabouraud medium and cultured at 30°C for 24 h, washed three times with PBS (pH = 7.4) and resuspended. The final concentration of the bacterial solution was 1×10 5 CFU / mL. Guanidinated polyamino acid, amphotericin B (AmB) or fluconazole (FlC) were added to the centrifuge tube with bacterial solution and treated for 2, 5, 10, 20 and 30 min respectively. At each time point, 100.0 μL of the mixture was dropped onto the agar plate and spread evenly, incubated at 30°C for 24 h, and the bactericidal rate of cationic polyamino acid was calculated by colony counting. The results are shown in Figure 6 As shown, Figure 6 is the number of colonies at different time points after treatment with the guanidinium polyamino acid in Example 35. The results show that the guanidinium polyamino acid has rapid bactericidal kinetics.

[0280] The above embodiments are only used to help understand the method and core idea of ​​the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A polyamino acid, characterized in that The structure is shown in formula (I): Formula (I); Among them, 10≤n≤100, 2≤m≤10; R1 is selected from , R2 is selected from phenyl or methyl, and x is selected from an integer between 1-6.

2. The polyamino acid according to claim 1, characterized in that The n is selected from 10, 20, 40 or 100; The m is selected from 2, 4, 6, 8 or 10; The x is selected from 1, 4, 5 or 6.

3. The polyamino acid according to claim 1, characterized in that The polyamino acid is selected from any of the following structures: 。 4. The method for preparing a polyamino acid according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) mixing the poly(β-benzyl aspartic acid) represented by formula (II), the diamine compound represented by formula (III) and a solvent to obtain a monoamine polyamino acid represented by formula (IV); (2) reacting a monoamine polyamino acid and 1H-pyrazole-1-carboxamidine hydrochloride under the catalysis of N, N-diisopropylethylamine to obtain a polyamino acid represented by formula (I); Formula (II); Formula (III); Formula (IV); Wherein, y is selected from an integer between 2-10.

5. The preparation method according to claim 4, characterized in that: In the step (1), the molar ratio of the side chain benzyl group of the poly(β-benzyl aspartic acid) to the diamine compound is 1:(10-50).

6. The preparation method according to claim 4, characterized in that: The solvent in step (1) is selected from one or more of N-methylpyrrolidone, dimethyl sulfoxide, and N,N-dimethylformamide; The reaction temperature in step (1) is 20°C-50°C; The reaction time is 1-6 h.

7. The preparation method according to claim 4, characterized in that: In the step (2), the mass ratio of monoamino polyamino acid to 1H-pyrazole-1-carboxamidine hydrochloride is 1:(1-2); In the step (2), the mass ratio of the monoamino polyamino acid to N, N-diisopropylethylamine is 1:(2-4).

8. The preparation method according to claim 4, characterized in that: The solvent for the reaction in step (2) is selected from a mixed solution of methanol and water; The reaction temperature in step (2) is 40°C-65°C; The reaction time in step (2) is 20-30 h.

9. The preparation method according to claim 4, characterized in that: The poly (β-benzyl aspartic acid) is prepared by ring-opening polymerization of β-benzyl aspartic acid-N-carboxyl cyclic anhydride under the action of an initiator; The initiator is selected from , R2 is selected from phenyl or methyl, and x is selected from an integer between 1-6.

10. Use of the polyamino acid according to any one of claims 1 to 3 and the polyamino acid prepared by the preparation method according to any one of claims 4 to 9 in the preparation of antibacterial drugs.

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