A polyamino acid, its preparation method and application

Abstract

The present invention discloses a polyamino acid, a preparation method and an application thereof, belonging to the technical field of antibacterial polyamino acids. The polyamino acid has a structure as shown in formula (I). Among them, 10 ≤ n ≤ 100, 2 ≤ m ≤ 10; R1 is selected from, R2 is selected from phenyl or methyl, and x is an integer between 1 and 6. The polyamino acid overcomes the limitations of natural antibacterial peptides in terms of salt sensitivity in complex physiological environments and a decrease in activity in a multivalent cation environment through the combined action of strategies for guanidinylation, regulation of the degree of polymerization, and side chain length, significantly improving the antibacterial activity and stability of the polyamino acid in complex environments, so that the polyamino acid has excellent broad-spectrum antibacterial properties, biocompatibility, biodegradability, and long-lasting and stable antibacterial performance. Formula (I).

Description

Technical Field

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

[0002] In recent years, antibacterial polyamino acids that mimic the structural characteristics of antibacterial peptides (such as positive charges and hydrophobic structures) have shown great potential in the treatment of multi-drug resistant microbial infections. First, the tunability of polyamino acids enables them to adjust the amino acid sequence and structure as needed, optimize the antibacterial effect, and improve the targeting against specific pathogenic microorganisms. This designability makes polyamino acids more flexible in diverse applications. Second, polyamino acids usually have good stability. Through the synthesis process, more stable and persistent peptide chain structures can be designed, avoiding the problem that natural antibacterial peptides lose their activity due to being easily degraded by proteases. Moreover, the production cost of polyamino acids is relatively low. Since they can be produced on a large scale by the living polymerization method of α-amino acid-N-carboxylic acid cyclic anhydride (NCA) monomers, the cost is more economical than that of natural antibacterial peptides, facilitating commercial applications. Polyamino acids can also overcome the problem of poor toxicity selectivity of natural peptides by changing their structures, improving the selectivity and safety against target bacteria. In the research field of antibacterial polyamino acids, most of the existing research focuses on polymerizing and modifying certain amino acids (such as histidine, lysine, arginine, glutamic acid, etc.) to form polymer materials with antibacterial properties. These amino acids, due to their cationicity or amphiphilicity, can disrupt the membrane structure through electrostatic interaction with the bacterial membrane, showing significant antibacterial activity. For example, the amino groups of lysine and arginine can enhance the binding force with the bacterial membrane, thus effectively inhibiting bacterial growth. However, the stability of these antibacterial polyamino acids is usually poor, and in a high-salt or high-concentration ion environment, the antibacterial performance of the polymer is likely to decrease. Although antibacterial polyamino acids show good antibacterial activity against some specific microorganisms (such as Escherichia coli, Staphylococcus aureus), their broad-spectrum antibacterial ability against a variety of different pathogenic bacteria is still insufficient, especially the effect against fungi is relatively limited.

[0003] Although certain achievements have been made in existing research, the research on antibacterial polyamino acid materials with aspartic acid as the backbone is relatively scarce. Aspartic acid has the characteristics of negatively charged amino acids, and its application in antibacterial polymers is relatively limited. Therefore, how to effectively utilize aspartic acid as the backbone to design new antibacterial polyamino acid materials and overcome the possible performance limitations remains a key issue in current research. Different from common antibacterial polyamino acid precursors such as poly(benzyl glutamate), poly(benzyl aspartate) can effectively avoid the problem of main chain breakage during aminolysis modification. Poly(benzyl glutamate) often undergoes main chain breakage during aminolysis modification, affecting the structural stability of the polymer. In contrast, poly(benzyl aspartate) can achieve quantitative modification during the modification process, and its main chain is not easily broken, maintaining good structural stability. In addition, aspartic acid residues can undergo structural transformation during aminolysis, introducing different configurations and sequences into the polymer main chain. Through the advantages of this quantitative modification and structural transformation, poly(benzyl aspartate) as a precursor of antibacterial polymers can not only maintain structural stability but also optimize antibacterial performance, opening up a new direction for the design and application of antibacterial polyamino acids.

[0004] Existing antibacterial materials are mainly prepared by guanidylation 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 processes of these materials are complex, the yields are low, and the modification of polyamino acid side chains is difficult, which is not conducive to cost control and large-scale production. The most crucial point is that although these materials have certain antibacterial effects, their antibacterial performance is still limited, especially the effects on broad-spectrum pathogens (Gram-negative bacteria, Gram-positive bacteria, fungi) are not ideal, resulting in limited actual application scope. For example, the minimum inhibitory concentration (MIC) against Candida albicans is generally greater than 20 μg / mL, and at the same time, they have high toxicity to normal cells, resulting in a low selectivity index (SI) of antibacterial polyamino acids and making it difficult to achieve a balance between safety and antibacterial performance. In addition, their antibacterial performance often significantly decreases in a high-salt environment, lacking anti-salt sensitivity design and limiting the 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 anti-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 its preparation method and application. The polyamino acid has excellent broad-spectrum antibacterial ability, long-lasting and stable antibacterial performance, and good biocompatibility.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] The present invention provides a polyamino acid, the structure of which is shown in formula (I):

[0009]

[0010] Formula (I);

[0011] wherein, 10 ≤ n ≤ 100, 2 ≤ m ≤ 10;

[0012] R1 is selected from , R2 is selected from phenyl or methyl, and x is an integer between 1 and 6.

[0013] In the structure of formula (I), the slashes on the main chain represent two different sequence arrangements of aspartic acid residues in the polyamino acid main chain, and the wavy lines in R1 represent the connection positions.

[0014] The guanidine group in the polyamino acid of the present invention provides it with strong hydrogen bond donor and acceptor capabilities and multi-point interactions, ensuring the stability of the antibacterial performance of the polyamino acid. At the same time, by regulating the degree of polymerization and side chain length of the polyamino acid, the molecular structure is optimized, thereby improving the salt tolerance of the polyamino acid.

[0015] The polyamino acid of 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). It can destroy the integrity of bacterial and fungal cell membranes through physical interactions, showing the characteristics of quickly killing bacteria and fungi.

[0016] Moreover, at a concentration of 2×MIC, the polyamino acid can inhibit the fungal survival rate to less than 5% within 5 minutes. In a salt environment, compared with monoamino polyamino acids, the minimum inhibitory concentration (MIC) of the polyamino acid (guanidinated polyamino acid) of the present invention against bacteria only increases slightly.

[0017] Preferably in the present invention, n is selected from 10, 20, 40, or 100;

[0018] Preferably, m is selected from 2, 4, 6, 8, or 10;

[0019] Preferably, x is selected from 1, 4, 5, or 6.

[0020] More preferably in the present invention, the polyamino acid is selected from any of the following structures:

[0021]

[0022]

[0023]

[0024]

[0025]

[0026]

[0027] 。

[0028] The present invention also provides a method for preparing the above polyamino acid, comprising the following steps:

[0029] (1) Mixing and reacting poly(β-benzyl aspartic acid) represented by formula (II), a diamino compound represented by formula (III) and a solvent to obtain a monoamino polyamino acid represented by formula (IV);

[0030] (2) Reacting the monoamino polyamino acid and 1H-pyrazole-1-carboxamidine hydrochloride under the catalysis of N,N-diisopropylethylamine to obtain the polyamino acid represented by formula (I);

[0031]

[0032] Formula (II);

[0033]

[0034] Formula (III);

[0035]

[0036] Formula (IV);

[0037] wherein y is an integer selected from 2 to 10.

[0038] Preferably in the present invention, the molar ratio of the benzyl side chain of poly(β-benzyl aspartic acid) to the diamino compound in step (1) is 1:(10 - 50); more preferably 1:(10 - 40). In some specific embodiments of the present invention, it is preferably 1:20.

[0039] Preferably in the present invention, the solvent in step (1) is selected from one or more of N-methylpyrrolidone, dimethyl sulfoxide, and N,N-dimethylformamide.

[0040] The present invention has no special limitation on the dosage of the above solvent, and it is only necessary to dissolve the poly(β-benzyl aspartic acid) and the diamino compound.

[0041] Preferably, the temperature of the reaction in step (1) is 20°C - 50°C; more preferably 20°C - 40°C. In some specific embodiments of the present invention, the temperature of the reaction is 25°C.

[0042] Preferably, the reaction time is 1 - 6 h; more preferably 2 - 4 h.

[0043] After the reaction in step (1) is completed, post-treatments such as dialysis and lyophilization are also included.

[0044] Preferably, in 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, it is preferably 1:2.

[0045] Preferably, in step (2), the mass ratio of the monoamino polyamino acid to N,N-diisopropylethylamine is 1:(2 - 4). In some specific embodiments of the present invention, it is preferably 1:2. Preferably, the reaction solvent in step (2) is selected from a mixed solution of methanol and water;

[0046] The volume of the mixed solution is preferably 0.1 - 3 mL.

[0047] The volume ratio of methanol to water in the mixed solution is (1 - 4):1.

[0048] Preferably, the temperature of the reaction 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.

[0049] Preferably, the reaction time in step (2) is 20 - 30 h; more preferably 22 - 26 h.

[0050] After the reaction in step (2) is completed, post-treatments such as sedimentation and drying are also included.

[0051] The solvent for sedimentation is selected from acetone.

[0052] The drying is preferably freeze-drying.

[0053] Preferably, the poly(β-benzyl aspartic acid) is prepared by ring-opening polymerization of β-benzyl aspartic acid-N-carboxy anhydride under the action of an initiator;

[0054] Preferably, the initiator is selected from , R2 is selected from phenyl or methyl, and x is 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.

[0055] The above initiator can be a common commercially available product.

[0056] The temperature of the ring-opening polymerization is preferably 20°C - 40°C; more preferably 20°C - 30°C.

[0057] The time of the ring-opening polymerization is preferably 2 - 5 d; more preferably 3 - 5 d.

[0058] The solvents for the ring-opening polymerization include but are not limited to anhydrous tetrahydrofuran, anhydrous N,N-dimethylformamide, anhydrous dichloromethane, etc.

[0059] The ratio of the total mass of the β-benzyl aspartic acid-N-carboxy anhydride and the initiator to the solvent for 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.

[0060] The molar ratio of the initiator to the β-benzyl aspartic acid-N-carboxy anhydride is 1 : (10 - 100).

[0061] After the ring-opening polymerization is completed, it also includes post-treatments such as dialysis and lyophilization.

[0062] The present invention has no special limitation on all the above post-treatments such as dialysis and lyophilization, and methods well-known to those skilled in the art can be used.

[0063] The present invention also provides the use of the above polyamino acid and the polyamino acid prepared by the above preparation method in the preparation of antibacterial drugs.

[0064] The polyamino acid described in the present invention is an antibacterial polyamino acid material with a hydrophobic chain as the end group and a guanidyl group as the side-chain cationic group, and has successfully achieved an efficient killing effect on the cell membranes of bacteria and fungi.

[0065] Since the polyamino acid contains a basic group amino in the side chain and is protonated with a large amount of positive charges under physiological conditions (neutral or weakly acidic pH) (referred to as cationic polyamino acid), it can quickly bind to the negatively charged bacterial cell membrane, ultimately leading to the death of bacteria and showing rapid bactericidal kinetics. And the polyamino acid has good biocompatibility. Therefore, the polyamino acid shows good application prospects when applied to antibacterial drugs.

[0066] Compared with the prior art, the polyamino acid provided by the present invention has a structure shown in formula (Ⅰ). Among them, 10 ≤ n ≤ 100, 2 ≤ m ≤ 10; R1 is selected from , R2 is selected from phenyl or methyl, and x is an integer between 1 and 6. The polyamino acid overcomes the salt sensitivity of natural antimicrobial peptides in complex physiological environments and the limitation of decreased activity in the environment of multivalent cations through the combined action of the strategies of guanidination, degree of polymerization, and side chain length regulation, significantly improving the antibacterial activity and stability of the polyamino acid in complex environments, making the polyamino acid have excellent broad-spectrum antibacterial properties, biocompatibility, degradability, and long-lasting and stable antibacterial performance. Description of the Drawings

[0067] Figure 1 1H NMR spectrum of poly(β-benzyl aspartic acid) prepared in Example 7;

[0068] Figure 2 1H NMR spectrum of monoamino polyamino acid prepared in Example 35;

[0069] Figure 3 1H NMR spectrum of the polyamino acid prepared in Example 35;

[0070] Figure 4 Inhibitory effect diagrams of the polyamino acid prepared in Example 35 on Staphylococcus aureus, Escherichia coli, and Candida albicans at different concentrations;

[0071] Figure 5 Scanning electron micrographs of Staphylococcus aureus, Escherichia coli, and Candida albicans after treatment with PBS or the cationic polyamino acid prepared in Example 35;

[0072] Figure 6 Bactericidal kinetic curve diagram of the polyamino acid prepared in Example 35 against Candida albicans. Detailed Embodiments

[0073] To further illustrate the present invention, the polyamino acid provided by the present invention, its preparation method and application will be described in detail below with reference to examples.

[0074] The source of the following β-benzyl aspartic acid-N-carboxy cyclic anhydride is not particularly limited. The synthesis can be carried out with reference to the method described in the literature published by B. A. Shidlovsky et al., B. A. Shidlovsky et. Al, J. Med. Chem. 1967, 10, 904–908.

[0075] The source of the following diamino compound is not particularly limited and can be generally commercially available.

[0076] The standard strains of Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) were purchased from Shandong Luwei Microbial Technology Co., Ltd.

[0077] The Candida albicans (ATCC 10231) was purchased from Qingdao Haibo Biotechnology Co., Ltd.

[0078] Example 1

[0079] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (Ⅱ), in which n = 10:

[0080] 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-carboxyanhydride, which was previously dissolved in 50 mL of anhydrous DMF, to it. After stirring and reacting at 25 °C for 72 h, dialysis and freeze-drying were carried out to obtain the white powder product n-pentylamine-poly(β-benzyl aspartic acid).

[0081]

[0082] Example 2

[0083] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (Ⅱ), in which n = 20:

[0084] 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-carboxyanhydride, which was previously dissolved in 50 mL of anhydrous DCM, to it. After stirring and reacting at 25 °C for 72 h, dialysis and freeze-drying were carried out to obtain the white powder product n-pentylamine-poly(β-benzyl aspartic acid).

[0085]

[0086] Example 3

[0087] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (Ⅱ), in which n = 40:

[0088] 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-carboxyanhydride, which was previously dissolved in 100 mL of anhydrous DCM, to it. After stirring and reacting at 25 °C for 72 h, dialysis and freeze-drying were carried out to obtain the white powder product n-pentylamine-poly(β-benzyl aspartic acid).

[0089]

[0090] Example 4

[0091] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (II), in which n = 100:

[0092] 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-carboxyanhydride, which has been previously dissolved in 200 mL of anhydrous DCM, to it. After stirring and reacting at 25 °C for 72 h, dialyze and lyophilize to obtain the white powder product n-pentylamine-poly(β-benzyl aspartic acid).

[0093]

[0094] Example 5

[0095] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (II), in which n = 10:

[0096] 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-carboxyanhydride, which has been previously dissolved in 50 mL of anhydrous DMF, to it. After stirring and reacting at 25 °C for 72 h, dialyze and lyophilize to obtain the white powder product n-hexylamine-poly(β-benzyl aspartic acid).

[0097]

[0098] Example 6

[0099] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (II), in which n = 20:

[0100] 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-carboxyanhydride, which has been previously dissolved in 50 mL of anhydrous DCM, to it. After stirring and reacting at 25 °C for 72 h, dialyze and lyophilize to obtain the white powder product n-hexylamine-poly(β-benzyl aspartic acid).

[0101]

[0102] Example 7

[0103] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (II), in the structure of formula (II), n = 40:

[0104] 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-carboxyanhydride, which has been previously dissolved in 100 mL of anhydrous DCM, to it. After stirring and reacting at 25 °C for 72 h, perform dialysis and then freeze-dry to obtain the white powder product n-hexylamine-poly(β-benzyl aspartic acid).

[0105]

[0106] Example 8

[0107] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (II), in the structure of formula (II), n = 100:

[0108] 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-carboxyanhydride, which has been previously dissolved in 100 mL of anhydrous DCM, to it. After stirring and reacting at 25 °C for 72 h, perform dialysis and then freeze-dry to obtain the white powder product n-hexylamine-poly(β-benzyl aspartic acid).

[0109]

[0110] Example 9

[0111] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (II), in the structure of formula (II), n = 10:

[0112] 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-carboxyanhydride, which has been previously dissolved in 50 mL of anhydrous DMF, to it. After stirring and reacting at 25 °C for 72 h, perform dialysis and then freeze-dry to obtain the white powder product n-heptylamine-poly(β-benzyl aspartic acid).

[0113]

[0114] Example 10

[0115] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (II), in the structure of formula (II), n = 20:

[0116] 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 compound β-benzyl aspartic acid-N-carboxy anhydride, which has been previously dissolved in 50 mL of anhydrous DCM, to it. After stirring the reaction at 25 °C for 72 h, dialyze and freeze-dry to obtain the white powder product n-heptylamine-poly(β-benzyl aspartic acid).

[0117]

[0118] Example 11

[0119] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (Ⅱ), in the structure of formula (Ⅴ), n = 40:

[0120] 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 compound β-benzyl aspartic acid-N-carboxy anhydride, which has been previously dissolved in 100 mL of anhydrous DCM, to it. After stirring the reaction at 25 °C for 72 h, dialyze and freeze-dry to obtain the white powder product n-heptylamine-poly(β-benzyl aspartic acid).

[0121]

[0122] Example 12

[0123] Synthesis of poly(β-benzyl aspartic acid) with the structure of formula (Ⅱ), in the structure of formula (Ⅱ), n = 100:

[0124] 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 compound β-benzyl aspartic acid-N-carboxy anhydride, which has been previously dissolved in 200 mL of anhydrous DCM, to it. After stirring the reaction at 25 °C for 72 h, dialyze and freeze-dry to obtain the white powder product n-heptylamine-poly(β-benzyl aspartic acid).

[0125]

[0126] Example 13

[0127] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10;

[0128] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 1 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0129] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.64 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, and stir until dissolved. After sealing, react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0130]

[0131] Example 14

[0132] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0133] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 1 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0134] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.54 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, and stir until dissolved. After sealing, react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0135]

[0136] Example 15

[0137] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0138] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 1 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0139] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.47 mmol of amino groups), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0140]

[0141] Example 16

[0142] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0143] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 1 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0144] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.41 mmol of amino groups), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0145]

[0146] Example 17

[0147] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0148] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 1 (the side groups contain a total of 0.98 mmol of benzyl), then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

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

[0150]

[0151] Example 18

[0152] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0153] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 2 (the side groups contain a total of 0.98 mmol of benzyl), then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0154] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.64 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0155]

[0156] Example 19

[0157] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0158] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 2 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0159] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.54 mmol of amino groups), 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0160]

[0161] Example 20

[0162] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0163] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 2 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0164] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamino polyamino acid material with 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-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0165]

[0166] Example 21

[0167] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0168] Weigh 0.20 g (the side groups contain 0.98 mmol of 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 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 monoamino polyamino acid shown in formula (IV).

[0169] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamino polyamino acid material with 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-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0170]

[0171] Example 22

[0172] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0173] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 2 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0174] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.37 mmol of amino groups), 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0175]

[0176] Example 23

[0177] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0178] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 3 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0179] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.64 mmol of amino groups), 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0180]

[0181] Example 24

[0182] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0183] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 3 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0184] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.54 mmol of amino groups), 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0185]

[0186] Example 25

[0187] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0188] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 3 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0189] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.47 mmol of amino groups), 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0190]

[0191] Example 26

[0192] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0193] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 3 (the side groups contain 0.98 mmol of benzyl in total), then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0194] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.41 mmol of amino groups in total), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0195]

[0196] Example 27

[0197] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0198] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 3 (the side groups contain 0.98 mmol of benzyl in total), then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0199] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.37 mmol of amino groups in total), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0200]

[0201] Example 28

[0202] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0203] Weigh 0.20 g of poly(β-benzyl aspartate) obtained in Example 4 (the side groups contain 0.98 mmol of benzyl in total), then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0204] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.64 mmol of amino groups in total), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0205]

[0206] Example 29

[0207] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0208] Weigh 0.20 g of poly(β-benzyl aspartate) obtained in Example 4 (the side groups contain 0.98 mmol of benzyl in total), then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0209] Weigh 0.10 g (the side groups contain 0.54 mmol of amino groups in total) of the monoamino polyamino acid material with 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-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0210]

[0211] Example 30

[0212] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0213] Weigh 0.20 g (the side groups contain 0.98 mmol of 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 monoamino polyamino acid shown in formula (IV).

[0214] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamino polyamino acid material with 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-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0215]

[0216] Example 31

[0217] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0218] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 4 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0219] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.41 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, and stir until dissolved. After sealing, react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0220]

[0221] Example 32

[0222] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0223] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 4 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

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

[0225]

[0226] Example 33

[0227] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0228] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 5 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0229] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.64 mmol of amino groups), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0230]

[0231] Example 34

[0232] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0233] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 5 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0234] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.54 mmol of amino groups), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0235]

[0236] Example 35

[0237] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0238] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 5 (the side groups contain 0.98 mmol of benzyl in total), then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0239] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.47 mmol of amino groups in total), 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0240]

[0241] Example 36

[0242] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0243] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 5 (the side groups contain 0.98 mmol of benzyl in total), then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0244] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.41 mmol of amino groups in total), 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0245]

[0246] Example 37

[0247] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0248] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 5 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0249] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.37 mmol of amino groups), 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0250]

[0251] Example 38

[0252] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0253] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 6 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0254] Weigh 0.10 g (the side groups contain a total of 0.64 mmol of amino groups) of the monoamino polyamino acid material with 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-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0255]

[0256] Example 39

[0257] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0258] Weigh 0.20 g (the side groups contain a total of 0.98 mmol of benzyl groups) 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 monoamino polyamino acid shown in formula (IV).

[0259] Weigh 0.10 g (the side groups contain a total of 0.54 mmol of amino groups) of the monoamino polyamino acid material with 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-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0260]

[0261] Example 40

[0262] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0263] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 6 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0264] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.47 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, and stir until dissolved. After sealing, react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0265]

[0266] Example 41

[0267] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0268] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 6 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0269] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.41 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, and stir until dissolved. After sealing, react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0270]

[0271] Example 42

[0272] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0273] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 6 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0274] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.37 mmol of amino groups), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0275]

[0276] Example 43

[0277] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0278] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 7 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0279] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.64 mmol of amino groups), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0280]

[0281] Example 44

[0282] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0283] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 7 (the side groups contain 0.98 mmol of benzyl in total), then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0284] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.54 mmol of amino groups in total), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0285]

[0286] Example 45

[0287] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0288] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 7 (the side groups contain 0.98 mmol of benzyl in total), then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0289] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.47 mmol of amino groups in total), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0290]

[0291] Example 46

[0292] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0293] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 7 (the side groups contain a total of 0.98 mmol of benzyl), then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0294] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.41 mmol of amino groups), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0295]

[0296] Example 47

[0297] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0298] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 7 (the side groups contain a total of 0.98 mmol of benzyl), then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0299] Weigh 0.10 g (the side groups contain 0.37 mmol of amino groups in total) of the monoamino polyamino acid material with 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-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0300]

[0301] Example 48

[0302] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0303] Weigh 0.20 g (the side groups contain 0.98 mmol of 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 lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0304] Weigh 0.10 g (the side groups contain 0.64 mmol of amino groups in total) of the monoamino polyamino acid material with 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-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0305]

[0306] Example 49

[0307] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0308] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 8 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0309] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.54 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, and stir until dissolved. After sealing, react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0310]

[0311] Example 50

[0312] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0313] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 8 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0314] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.47 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol containing 0.3 mL of N,N-diisopropylethylamine, and stir until dissolved. After sealing, react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0315]

[0316] Example 51

[0317] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0318] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 8 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0319] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.41 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0320]

[0321] Example 52

[0322] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0323] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 8 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0324] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.37 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0325]

[0326] Example 53

[0327] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0328] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 9 (the side groups contain 0.98 mmol of benzyl in total), then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0329] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.64 mmol of amino groups in total), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0330]

[0331] Example 54

[0332] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0333] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 9 (the side groups contain 0.98 mmol of benzyl in total), then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0334] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.54 mmol of amino groups in total), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0335]

[0336] Example 55

[0337] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0338] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 9 (the side groups contain 0.98 mmol of benzyl in total), then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0339] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.47 mmol of amino groups in total), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0340]

[0341] Example 56

[0342] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0343] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 9 (the side groups contain 0.98 mmol of benzyl in total), then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0344] Weigh 0.10 g (the side groups contain a total of 0.41 mmol of amino groups) of the monoamino polyamino acid material with 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-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0345]

[0346] Example 57

[0347] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 10:

[0348] Weigh 0.20 g (the side groups contain a total of 0.98 mmol of benzyl groups) 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 monoamino polyamino acid shown in formula (IV).

[0349] Weigh 0.10 g (the side groups contain a total of 0.37 mmol of amino groups) of the monoamino polyamino acid material with 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-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0350]

[0351] Example 58

[0352] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0353] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 10 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0354] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.64 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0355]

[0356] Example 59

[0357] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 20:

[0358] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 10 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0359] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.54 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0360]

[0361] Example 60

[0362] Synthesis of guanidinated polyamino acid with the structure of formula (I), where n = 20 in the structure of formula (I):

[0363] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 10 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0364] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.47 mmol of amino groups), 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0365]

[0366] Example 61

[0367] Synthesis of guanidinated polyamino acid with the structure of formula (I), where n = 20 in the structure of formula (I):

[0368] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 10 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0369] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.41 mmol of amino groups), 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, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0370]

[0371] Example 62

[0372] Synthesis of guanidinated polyamino acid with the structure of formula (I), in which n = 20 in the structure of formula (I):

[0373] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 10 (the side groups contain 0.98 mmol of benzyl in total), then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0374] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.37 mmol of amino groups in total), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0375]

[0376] Example 63

[0377] Synthesis of guanidinated polyamino acid with the structure of formula (I), in which n = 40 in the structure of formula (I):

[0378] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 11 (the side groups contain 0.98 mmol of benzyl in total), then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0379] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.64 mmol of amino groups in total), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0380]

[0381] Example 64

[0382] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0383] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 11 (the side groups contain 0.98 mmol of benzyl in total), then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0384] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.54 mmol of amino groups in total), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0385]

[0386] Example 65

[0387] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0388] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 11 (the side groups contain 0.98 mmol of benzyl in total), then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0389] Weigh 0.10 g (the side groups contain 0.47 mmol of amino groups in total) of the monoamino polyamino acid material with 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-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0390]

[0391] Example 66

[0392] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0393] Weigh 0.20 g (the side groups contain 0.98 mmol of 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 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 lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0394] Weigh 0.10 g (the side groups contain 0.41 mmol of amino groups in total) of the monoamino polyamino acid material with 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-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0395]

[0396] Example 67

[0397] Synthesis of guanidinylated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 40:

[0398] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 11 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0399] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.37 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0400]

[0401] Example 68

[0402] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0403] Weigh 0.20 g of the poly(β-benzyl aspartic acid) obtained in Example 12 (the side groups contain a total of 0.98 mmol of benzyl groups), then add 1.17 g (19.51 mmol) of ethylenediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0404] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain a total of 0.64 mmol of amino groups), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide 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, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0405]

[0406] Example 69

[0407] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0408] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 12 (the side groups contain 0.98 mmol of benzyl groups in total), then add 1.72 g (19.51 mmol) of 1,4-butanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0409] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.54 mmol of amino groups in total), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0410]

[0411] Example 70

[0412] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0413] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 12 (the side groups contain 0.98 mmol of benzyl groups in total), then add 2.27 g (19.51 mmol) of 1,6-hexanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and lyophilize to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0414] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.47 mmol of amino groups in total), 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 dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and lyophilize to obtain a white powdery polyamino acid material with the following structure.

[0415]

[0416] Example 71

[0417] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0418] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 12 (the side groups contain 0.98 mmol of benzyl in total), then add 2.81 g (19.51 mmol) of 1,8-octanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0419] Weigh 0.10 g of the monoamino polyamino acid material with the structure of formula (IV) prepared above (the side groups contain 0.41 mmol of amino groups in total), dissolve it in 2 mL of deionized water, add 0.2 g (1.36 mmol) of 1H-pyrazole-1-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0420]

[0421] Example 72

[0422] Synthesis of guanidinated polyamino acid with the structure of formula (I), in the structure of formula (I), n = 100:

[0423] Weigh 0.20 g of poly(β-benzyl aspartic acid) obtained in Example 12 (the side groups contain 0.98 mmol of benzyl in total), then add 3.36 g (19.51 mmol) of 1,10-decanediamine, and then add 5 mL of anhydrous DMSO and stir until dissolved. After sealing, react at 25 °C for 2 h. After the reaction stops, dialyze and freeze-dry to obtain a white powdery material, which is the monoamino polyamino acid shown in formula (IV).

[0424] Weigh 0.10 g (the side groups contain 0.37 mmol of amino groups in total) of the monoamino polyamino acid material with 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-carboximidamide hydrochloride and 0.4 mL of methanol dissolved with 0.3 mL of N,N-diisopropylethylamine, stir until dissolved, seal and react at 55 °C for 24 h. After the reaction stops, precipitate with acetone and dissolve with methanol, repeat three times, and freeze-dry to obtain a white powdery polyamino acid material with the following structure.

[0425]

[0426] Performance test experiments

[0427] (1) Conduct structure detection on the polyamino acid materials with the structures of formula (I), formula (II), and formula (IV) obtained in the above examples.

[0428] Figure 1 1H NMR spectrum of poly(β-benzyl aspartic acid) shown in formula (II) prepared in Example 7.

[0429] Figure 2 1H NMR spectrum of the monoamino polyamino acid prepared in Example 35. It can be seen from Figure 2 that the side groups of poly(β-benzyl aspartic acid) have been successfully bonded with monoamino groups, and a monoamino polyamino acid with the structure of formula (IV) is obtained.

[0430] Figure 3 1H NMR spectrum of the guanidinylated polyamino acid prepared in Example 35. It can be seen from Figure 3 that the side groups of the monoamino polyamino acid with the structure of formula (IV) have been successfully bonded with guanidyl groups, and a guanidinylated polyamino acid with the structure of formula (I) is obtained.

[0431] (2) Test the inhibition of different bacteria at different concentrations.

[0432] The results of the inhibition of different bacteria by the guanidinylated polyamino acid with the structure of formula (I) prepared in Example 35 at different concentrations are as shown in Figure 4 shown.

[0433] (3) In vitro antibacterial activity detection experiment of guanidinylated polyamino acid (microplate method)

[0434] Co-culture the guanidine antibacterial polyamino acid with the structure of formula (I) with Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), and Candida albicans (ATCC 10231), and detect its minimum inhibitory concentration (MIC):

[0435] First, Staphylococcus aureus and Escherichia coli were inoculated in fresh MH medium and cultured at 37 °C for 10 h. Bacteria in the logarithmic phase were taken and diluted with fresh MH medium, and the bacteria (100 µL, 1×10 6 CFU / mL) were added to a 96-well plate. The polyamino acid (guanidinated polyamino acid) material of the present invention was diluted using the serial dilution method. Then, PBS (pH = 7.4) as the control group and the diluted guanidine polyamino acid material (100 µL) were respectively added to the 96-well plate. The microplate reader was used to shake for 60 s to mix them evenly, and the optical density at 600 nm was measured. The culture plate was cultured at 37 °C for 24 h, and then the optical density of the microbial solution was measured at 600 nm. The MIC is the lowest concentration at which no bacterial growth is detected. Candida albicans was inoculated in fresh Sabouraud medium and cultured at 30 °C for 24 h. Fungi in the logarithmic phase were taken and diluted with fresh RPMI-1640 medium, and the bacteria (100 µL, 1×10 5 CFU / mL) were added to a 96-well plate. The remaining operations were similar to the above.

[0436] (IV) Measuring the stability (salt resistance sensitivity) of the MIC of guanidinated polyamino acid in a salt environment

[0437] The method was as follows: NaCl was added to the medium to adjust the concentration of NaCl to 0.09 g / mL to simulate a high-salt environment. The MIC of guanidinated polyamino acid in this environment was measured and compared with the MIC in a normal environment (without NaCl). If the MIC in the high-salt environment is similar to or not much different from the MIC in the normal environment, it indicates that the polyamino acid has good salt resistance sensitivity.

[0438] The results of the minimum inhibitory concentration test and salt resistance sensitivity test for different bacteria are shown below:

[0439] (1) The results of the minimum inhibitory concentration of the guanidinated polyamino acid with the structure of formula (I) prepared in Example 35 against different bacteria are shown in Table 1.

[0440] Table 1 Minimum inhibitory concentration (MIC, µg / mL) of the polyamino acid prepared in Example 35 against different bacteria

[0441]

[0442] Note: a Indicates determination in a simulated high-salt environment with 0.09 g / mL NaCl.

[0443] Table 1 results show that the minimum inhibitory concentration (MIC) of the monoamino polyamino acid prepared in Example 35 against Staphylococcus aureus is 7.8 μg / mL, and the MIC against Escherichia coli is 7.8 μg / mL, but it has no antifungal ability. While the guanidinylated polyamino acid material prepared in Example 35 has good antibacterial activity against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Candida albicans (ATCC 10231), and its MIC is between 3.9 - 7.8 μg / mL, showing more excellent broad-spectrum antibacterial activity. In addition, simulating a high-salt environment in an NaCl solution, the MIC of the monoamino polyamino acid prepared in Example 35 against Staphylococcus aureus is 250 μg / mL, and the MIC against Escherichia coli is 500 μg / mL, which is increased by more than 30 times. While the MIC of the guanidinylated polyamino acid prepared in Example 35 against the three bacteria only slightly increases by 1 - 4 times, indicating its salt resistance sensitivity.

[0444] (2) The results of the minimum inhibitory concentration of the guanidinylated polyamino acid with the structure of formula (I) prepared in Example 13 against different bacteria are shown in Table 2.

[0445] Table 2 Minimum inhibitory concentration (MIC, μg / mL) of the polyamino acid prepared in Example 13 against different bacteria

[0446]

[0447] Note: a It indicates that the measurement was carried out in a 0.09 g / mL NaCl solution to simulate a high-salt environment.

[0448] Table 2 results show that the MIC of the monoamino polyamino acid prepared in Example 13 against Staphylococcus aureus is 62.5 μg / mL, and the MIC against Escherichia coli is 125 μg / mL, showing weak antibacterial activity and no antifungal ability. While the polyamino acid (guanidinylated 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 - 15.6 μg / mL, indicating its broad-spectrum antibacterial activity. In addition, simulating a high-salt environment in an NaCl solution, the monoamino polyamino acid prepared in Example 13 loses its antibacterial activity, and the MIC against bacteria is greater than 500 μg / mL. While for the guanidinylated polyamino acid prepared in Example 13 in a high-salt environment, the MIC increases from 7.8 - 15.6 μg / mL to 31.2 - 62.5 μg / mL, and the antibacterial activity slightly decreases, indicating its salt resistance sensitivity.

[0449] (3)The results of the minimum inhibitory concentrations of the guanidinylated polyamino acids with the structure of formula (I) prepared in Example 72 against different bacteria are shown in Table 3.

[0450] Table 3 Minimum inhibitory concentrations (MIC, μg / mL) of the antibacterial polyamino acids in Example 72 against different bacteria

[0451]

[0452] Note: a Indicates determination in a 0.09 g / mL NaCl solution, simulating a high-salt environment.

[0453] The results in Table 3 show that for the monoamino polyamino acids prepared in Example 72, in a normal environment or a high-salt environment, the MIC against Staphylococcus aureus and Escherichia coli is 7.8 μg / mL. Their antibacterial effects on the two bacteria are salt-sensitive. However, in a normal environment, they have a weak inhibitory ability against Candida albicans with an MIC of 125 μg / mL, and their antifungal ability is lost in a high-salt environment. The guanidinylated polyamino acid materials prepared in Example 72 have significant antibacterial activity against Staphylococcus aureus (ATCC25923), Escherichia coli (ATCC 25922), and Candida albicans (ATCC 10231), with their MICs between 1.8 and 3.9 μg / mL, showing broad-spectrum antibacterial activity. In addition, in a high-salt environment, the MICs of the highly polymerized guanidinylated polyamino acids prepared in Example 72 against the three bacteria do not change, indicating their salt-insensitivity.

[0454] (5) Test on the ability of guanidinylated polyamino acids to disrupt the cell membranes of bacteria

[0455] Verification was carried out by using a scanning electron microscope to photograph the cell membrane morphology of bacteria after treatment with the polyamino acid (guanidinylated polyamino acid) material prepared in Example 35:

[0456] 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 suspension was 2×10 6 CFU / mL. 500.0 μL of the bacterial suspension was mixed evenly with 500.0 μL of a guanidinylated polyamino acid solution with a concentration of 15.6 μg / mL, incubated at 37 °C for 30 min, and then the treated bacterial samples were collected by centrifugation and washed twice with PBS.

[0457] Next, it was fixed with a 4% paraformaldehyde solution at 25 °C for 5 h.

[0458] Subsequently, the samples were washed once with PBS and dehydrated with a gradient of ethanol solutions (10%, 25%, 50%, 75%, 90% and 100%). Finally, the bacterial samples were dropped onto silicon wafers, 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 suspension was 2×10 5 CFU / mL. The remaining operations were similar to those for bacteria.

[0459] Figure 5 It is the morphology of bacteria after treatment with guanidinylated polyamino acids in Example 35. Figure 5 The results showed that the guanidinylated polyamino acids had good ability to disrupt bacterial cell membranes.

[0460] (VI) Bactericidal kinetics test of guanidinylated polyamino acids (fungal plate counting method)

[0461] 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 suspension was 1×10 5 CFU / mL. Guanidinylated polyamino acids, amphotericin B (AmB) or fluconazole (FlC) were added to the centrifuge tubes containing the bacterial suspension and treated for 2, 5, 10, 20 and 30 min respectively. At each time point, 100.0 μL of the mixture was taken and dropped onto an agar plate and spread evenly, and cultured at 30 °C for 24 h. The bactericidal rate of the cationic polyamino acids was calculated by colony counting. The results are as Figure 6 shown, Figure 6 It is the number of colonies at different time points after treatment with guanidine polyamino acids in Example 35. The results showed that the guanidinylated polyamino acids had rapid bactericidal kinetics.

[0462] The descriptions of the above embodiments are only used to help understand the method of the present invention and its core idea. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. A polyamino acid, characterized in that, The structure is as shown in formula (Ⅰ): Formula (I); Wherein, 10 ≤ n ≤ 100, 2 ≤ m ≤ 10; R1 is selected from , R2 is selected from methyl, and x is an integer between 4 and 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.

3. The polyamino acid according to claim 1, wherein 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, It includes the following steps: (1) Mix and react the poly(β-benzyl aspartic acid) shown in formula (Ⅱ), the diamino compound shown in formula (Ⅲ) and a solvent to obtain the monoamino polyamino acid shown in formula (Ⅳ); (2) React the monoamino polyamino acid and 1 H -pyrazole-1-carboxamidine hydrochloride under the catalysis of N, N -diisopropylethylamine to obtain the polyamino acid shown in formula (I); Formula (II); Formula (III); Formula (IV); Wherein, y is an integer between 2 and 10.

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

6. The preparation method according to claim 4, wherein The solvent in the step (1) is selected from N N-methylpyrrolidone, dimethyl sulfoxide, N,N N,N-dimethylformamide, or one or more thereof; In the step (1), the reaction temperature 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 the monoamino polyamino acid to 1 H- pyrazole-1-carboxamidine hydrochloride is 1:(1-2); In the step (2), the mass ratio of the monoamino polyamino acid and N, N -diisopropylethylamine is 1:(2 - 4).

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

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

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

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