Clustered peptide with side group containing functionalized diphenylamine group and preparation method of clustered peptide

Abstract

The invention provides a clustered peptide with a side group containing a functionalized diphenylamine group and a preparation method of the clustered peptide. The preparation method comprises the following steps: carrying out ring-opening polymerization reaction on N-thiocarboxylic acid anhydride containing bromophenyl groups under the action of an initiator to obtain a clustered peptide with a side group containing bromophenyl groups; in the presence of an inorganic base, a palladium catalyst and a ligand, a raw material system comprising a cluster peptide with a side group containing a bromophenyl group and an aromatic amine derivative is subjected to an amination coupling reaction to obtain the cluster peptide with a side group containing a functionalized diphenylamine group as shown in a structural formula (I), # imgabs0 #, in which R1 is any one of n-hexyl, benzyl, neopentyl and methoxy polyethylene glycol; r2 is any one of a hydrogen atom, an alkyl group, an alkoxy group, a phenyl group, a triphenyl vinyl group and a diazenyl phenyl group; n is an integer between 10 and 100; and x is 1 or 2. The preparation method is simple and easy to implement, has the advantages of high efficiency and high universality, and is suitable for wide popularization and application.

Description

Technical Field

[0001] The invention relates to the technical field of polymer synthesis, in particular to a polymerized peptide with a side group containing a functionalized diphenylamine group and a preparation method thereof. Background Art

[0002] Polypeptides are a new type of biopolymer material that mimics the structure of polypeptides. Its main chain is polyglycine, and the nitrogen atoms contain different substituents. Since the substituents of polypeptides are located on the nitrogen atoms, there is no intramolecular and intermolecular hydrogen bonding. Therefore, polypeptides have excellent biocompatibility, solubility and processability, and are widely used in nanoassembly and biomedical fields (Macromol. Rapid Commun. 2022, 441, 2200301; Eur. Polym. J. 2018, 109, 26-42). However, the side groups of the currently synthesized polypeptides are mainly alkyl and aromatic groups, and the performance is relatively single, which cannot meet the diversified and intelligent application requirements of polypeptide materials. Therefore, it is urgent to develop polypeptides with side group functionalization to meet market demand.

[0003] In the prior art, the synthesis of side-group functionalized polypeptides is usually achieved by the following method: designing and synthesizing N-carboxyanhydride (NCA) or N-thiocarboxylic anhydride (NTA) monomers containing functional side groups, and then ring-opening polymerization to obtain side-group functionalized polypeptides (Polym.C hem.2021, 1212, 1823-1829; Macromolecules 2020, 53 13, 5218-5226). However, this method requires the design of different monomer synthesis routes for different functional groups, which is relatively complicated and lacks universality.

[0004] Therefore, it is urgent to explore an efficient and universal method for preparing side-group functionalized peptides to meet market demand. Summary of the invention

[0005] The invention provides a method for preparing a polypeptide containing a functionalized diphenylamine group on a side group. The preparation method comprises the following steps: subjecting N-thiocarboxylic anhydride containing a bromophenyl group to a ring-opening polymerization reaction under the action of an initiator to obtain a polypeptide containing a bromophenyl group on a side group; and then post-modifying the side group of the polypeptide by an amination coupling reaction catalyzed by a palladium-based catalyst. The polypeptide containing a functionalized diphenylamine group on a side group can be efficiently prepared (with a yield of more than 84%). The preparation method is simple and easy to operate, has the advantages of high efficiency and strong universality, and is suitable for wide promotion and application.

[0006] The present invention also provides a peptide having a functionalized diphenylamine group on the side chain, which is prepared by the above preparation method. The synthetic route for preparing the peptide having a functionalized biphenyl group on the side chain is simple, the raw materials are easy to obtain, the cost is low and the yield is high.

[0007] The first aspect of the present invention provides a method for preparing a peptide having a functionalized diphenylamine group as a side group, comprising: subjecting an N-thiocarboxylic anhydride containing a bromophenyl group to a ring-opening polymerization reaction under the action of an initiator to obtain a peptide having a bromophenyl group as a side group;

[0008] In the presence of an inorganic base, a palladium catalyst and a ligand, a raw material system including the polypeptide containing a bromophenyl group on the side group and an aromatic amine derivative undergoes an amination coupling reaction to obtain a polypeptide containing a functionalized diphenylamine group on the side group. The polypeptide containing a functionalized diphenylamine group on the side group has a structural formula as shown in formula (I):

[0009]

[0010] Among them, R1 is any one of n-hexyl, benzyl, neopentyl, and methoxypolyethylene glycol; R2 is any one of hydrogen atom, alkyl, alkoxy, phenyl, triphenylvinyl, and diazenephenyl; n is an integer between 10 and 100; and x is 1 or 2.

[0011] In the method for preparing a peptide having a functionalized diphenylamine group as a side group, the molar ratio of the N-thiocarboxylic anhydride containing a bromophenyl group to the initiator is (10-100):1.

[0012] The method for preparing a polypeptide having a functionalized diphenylamine group as a side group as described above, wherein the inorganic base is one of potassium phosphate and cesium carbonate, the palladium catalyst is one of tris(dibenzylideneacetone)dipalladium and palladium acetate, and the ligand is one of 2-(dicyclohexylphosphino)biphenyl and 2-(di-tert-butylphosphino)biphenyl;

[0013] The molar ratio of the bromophenyl group, aromatic amine derivative, inorganic base, palladium catalyst and ligand in the polypeptide containing bromophenyl group on the side group is 1: (1-2): (2-4): (0.1-0.2): (0.4-0.6).

[0014] In the method for preparing a peptide having a functionalized diphenylamine group as a side group, the reaction temperature for the amination coupling reaction is 90° C. to 120° C. and the reaction time is 12 h to 36 h.

[0015] In the method for preparing the polypeptide having a functionalized diphenylamine group as a side group, the reaction temperature for the ring-opening polymerization reaction is 50° C. to 80° C., and the reaction time is 24 h to 96 h.

[0016] According to the method for preparing a peptide having a functionalized diphenylamine group as a side group, the N-thiocarboxylic acid anhydride containing a bromophenyl group is one of N-4-bromophenylmethylglycine-N-thiocarboxylic acid anhydride and N-4-bromophenylethylglycine-N-thiocarboxylic acid anhydride; the structural formula of the N-4-bromophenylmethylglycine-N-thiocarboxylic acid anhydride is shown in formula (II), and the structural formula of the N-4-bromophenylethylglycine-N-thiocarboxylic acid anhydride is shown in formula (III):

[0017]

[0018] In the method for preparing the polypeptide having a functionalized diphenylamine group as a side group, the structural formula of the aromatic amine derivative is any one of formula (IV), formula (V) and formula (VI):

[0019]

[0020] Among them, R3 is a hydrogen atom, an alkyl group, an alkoxy group or a phenyl group; R4 to R6 are independently selected from one of a hydrogen atom, an alkyl group, an alkoxy group or a phenyl group; R7 is a hydrogen atom, an alkyl group, an alkoxy group, a sulfonic acid group or a dimethylamino group.

[0021] The preparation method of the polypeptide containing a functionalized diphenylamine group on the side group as described above, the specific steps of performing the ring-opening polymerization reaction are: dissolving the N-thiocarboxylic anhydride containing a bromophenyl group in a first organic solvent to obtain a mixed solution, and then adding an initiator to the mixed solution, so that the N-thiocarboxylic anhydride containing a bromophenyl group undergoes a ring-opening polymerization reaction under the action of the initiator to obtain the polypeptide containing a bromophenyl group on the side group, or dissolving the N-thiocarboxylic anhydride containing a bromophenyl group and the initiator in a first organic solvent, so that the N-thiocarboxylic anhydride containing a bromophenyl group undergoes a ring-opening polymerization reaction under the action of the initiator to obtain the polypeptide containing a bromophenyl group on the side group;

[0022] The initiator is one of n-hexylamine, benzylamine, neopentylamine, and methoxy polyethylene glycol amine;

[0023] The first organic solvent is at least one of tetrahydrofuran, dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, tetramethylurea, acetonitrile, benzonitrile, toluene and chloroform.

[0024] The preparation method of the polypeptide containing a functionalized diphenylamine group on the side group as described above, the specific steps of the amination coupling reaction are: dissolving the polypeptide containing a bromophenyl group on the side group, an aromatic amine derivative, an inorganic base, a palladium catalyst and a ligand in a second organic solvent, and in the presence of the inorganic base, the palladium catalyst and the ligand, subjecting the raw material system including the polypeptide containing a bromophenyl group on the side group and the aromatic amine derivative to an amination coupling reaction to obtain the polypeptide containing a functionalized diphenylamine group on the side group;

[0025] The second organic solvent includes N,N-dimethylformamide.

[0026] The second aspect of the present invention provides a polymerized peptide having a side group containing a functionalized diphenylamine group, which is prepared by the above-mentioned method for preparing a polymerized peptide having a side group containing a functionalized diphenylamine group.

[0027] The present invention provides a method for preparing a peptide having a functionalized diphenylamine group on a side group. The method comprises the following steps: a ring-opening polymerization of an N-thiocarboxylic anhydride containing a bromophenyl group under the action of an initiator to obtain a peptide having a bromophenyl group on a side group; then, in the presence of a palladium catalyst, an inorganic base and a ligand, an amination coupling reaction is performed on a raw material system including the peptide having a bromophenyl group on a side group and an aromatic amine derivative to obtain a peptide having a functionalized diphenylamine group on a side group. The present invention utilizes an amination coupling reaction catalyzed by a palladium catalyst to post-modify the side group of the peptide having a bromophenyl group on a side group, and simultaneously introduces groups such as alkyl, alkoxy, phenyl and triphenylvinyl on the basis of forming a diphenylamine group, so as to efficiently prepare a peptide having a functionalized diphenylamine group on a side group (with a yield of more than 84%). The present invention uses an amination coupling reaction for post-modification of a peptide having a bromophenyl group on a side group, and is a novel method for preparing a peptide having a functionalized diphenylamine group on a side group. The raw materials of the preparation method provided by the present invention are widely available and can be obtained from existing commercial channels at low cost. In addition, the preparation method is simple and easy to implement, the conditions of the ring-opening polymerization reaction and the amination coupling reaction are mild, and there is no need to design different monomer synthesis routes for different functional groups. The method has the advantages of high efficiency and strong universality, and is suitable for wide promotion and application.

[0028] The polypeptide with a functionalized diphenylamine group in the side chain provided by the present invention is prepared by the above-mentioned preparation method. The synthetic route for preparing the polypeptide with a functionalized diphenylamine group in the side chain is simple, the raw materials are easy to obtain, the cost is low, and the yield is high. The structure and performance of the polypeptide with a functionalized diphenylamine group in the side chain are easy to control and can be adjusted by the functional group on the aromatic amine derivative. The polypeptide with a functionalized diphenylamine group in the side chain has broad application prospects in the fields of liquid crystal, fluorescence, nanoassembly, intelligent response, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The hydrogen nuclear magnetic spectrum of the α1-clustered peptide provided in Example 1 of the present invention;

[0030] Figure 2 The hydrogen nuclear magnetic spectrum of the α2-clustered peptide provided in Example 2 of the present invention;

[0031] Figure 3 The hydrogen nuclear magnetic spectrum of the α3-clustered peptide provided in Example 3 of the present invention;

[0032] Figure 4 The fluorescence spectrum of the α3-peptide provided in Example 3 of the present invention in a tetrahydrofuran / water mixed solution;

[0033] Figure 5 This is the hydrogen nuclear magnetic spectrum of the α4-clustered peptide provided in Example 4 of the present invention;

[0034] Figure 6 The ultraviolet-visible light absorption spectrum of the α4-clustered peptide provided in Example 4 of the present invention under different wavelength conditions; wherein, Figure 6 a is under the condition of 450nm wavelength; b is under the condition of 530nm wavelength;

[0035] Figure 7 This is the hydrogen nuclear magnetic spectrum of the α5-clustered peptide provided in Example 5 of the present invention;

[0036] Figure 8 The hydrogen nuclear magnetic spectrum of the α6-clustered peptide provided in Example 6 of the present invention;

[0037] Fig. 9 This is the hydrogen nuclear magnetic spectrum of the α7-clustered peptide provided in Example 7 of the present invention. DETAILED DESCRIPTION

[0038] In order to make the purpose, technical solutions and advantages of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0039] Unless otherwise specified, the raw materials and reagents used in the following examples can be obtained from commercial sources; the processes used, unless otherwise specified, are conventional processes in the art.

[0040] It should be noted that, in the present invention, there are descriptions involving “first”, “second”, etc., and the descriptions of “first”, “second”, etc. are only used for descriptive purposes and therefore cannot be understood as limitations on the present invention.

[0041] The terms described herein are used only to describe the embodiments and should not be construed to limit the invention as a whole.

[0042] As used herein, the term "N-thiocarboxylic anhydride containing a bromophenyl group" refers to N-4-bromophenylmethylglycine-N-thiocarboxylic anhydride or N-4-bromophenylethylglycine-N-thiocarboxylic anhydride. The N-4-bromophenylmethylglycine-N-thiocarboxylic anhydride and N-4-bromophenylethylglycine-N-thiocarboxylic anhydride used in the embodiments of the present invention are synthesized according to the method in the reference (European Polymer Journal, 2018, 109, 26-42; Acta Polym. Sin. 2022, 53 12, 1475-1483).

[0043] As used herein, the term "polypeptide containing bromophenyl groups in the side groups" refers to a synthetic polypeptide whose main chain is polyglycine and whose substituents on the nitrogen atom are 4-bromophenylmethyl or 4-bromophenylethyl. In other words, the term is used to indicate a polymer prepared from an N-thiocarboxylic anhydride monomer source containing bromophenyl groups. For example, poly (N-4-bromophenylmethylglycine), poly (N-4-bromophenylethylglycine), polyethylene glycol-b-poly (N-4-bromophenylethylglycine) in the embodiments of the present invention.

[0044] As used herein, the term "aromatic amine derivative" refers to a compound in which an amino group (-NH2) is attached to a benzene ring, and other atoms or groups are attached to the benzene ring.

[0045] The first aspect of the present invention provides a method for preparing a peptide having a functionalized diphenylamine group as a side group, comprising: subjecting an N-thiocarboxylic anhydride containing a bromophenyl group to a ring-opening polymerization reaction under the action of an initiator to obtain a peptide having a bromophenyl group as a side group;

[0046] In the presence of an inorganic base, a palladium catalyst and a ligand, a raw material system including the polypeptide containing a bromophenyl group on the side group and an aromatic amine derivative undergoes an amination coupling reaction to obtain a polypeptide containing a functionalized diphenylamine group on the side group. The polypeptide containing a functionalized diphenylamine group on the side group has a structural formula as shown in formula (I):

[0047]

[0048] Among them, R1 is any one of n-hexyl, benzyl, neopentyl, and methoxypolyethylene glycol; R2 is any one of hydrogen atom, alkyl, alkoxy, phenyl, triphenylvinyl, and diazenephenyl; n is an integer between 10 and 100; and x is 1 or 2.

[0049] The object of the present invention is to prepare a peptide having a functionalized diphenylamine group on the side group. Specifically, in the presence of an initiator, an amino group in the initiator nucleophilically attacks the carbonyl group at the 5th position of N-thiocarboxylic anhydride containing a bromophenyl group to cause a ring-opening polymerization reaction. The thiocarbamic acid group formed by the reaction is unstable, and after removing a molecule of carbonyl sulfide (COS), a new secondary amino group is formed, and the nucleophilic attack on the N-thiocarboxylic anhydride continues to open the ring for chain growth to obtain a peptide having a bromophenyl group on the side group; a palladium-based catalyst and a ligand form a palladium compound, and then the bromophenyl group in the peptide having a bromophenyl group on the side group and the palladium compound undergo an oxidative addition reaction to obtain an addition product; the addition product is coordinated with an aromatic amine derivative to obtain an intermediate; and then the intermediate is deprotonated and eliminated under the action of an inorganic base to obtain a peptide having a functionalized diphenylamine group on the side group.

[0050] The present invention uses a ring-opening polymerization reaction of N-thiocarboxylic anhydride containing a bromophenyl group to obtain a polypeptide containing a bromophenyl group on the side group, and then uses an amination coupling reaction catalyzed by a palladium-based catalyst to post-modify the side group of the polypeptide, so that the polypeptide containing a functionalized diphenylamine group on the side group can be efficiently prepared (with a yield of more than 84%). The present invention uses an amination coupling reaction for post-modification of polypeptides, which is a new method for preparing polypeptides with functionalized side groups. The raw materials of the preparation method provided by the present invention are widely available and can be obtained from existing commercial channels, with low cost; and the preparation method is simple and easy, the conditions of the ring-opening polymerization and the amination coupling reaction are mild, and it has the advantages of high efficiency and strong universality, and is suitable for wide promotion and application.

[0051] In a specific embodiment, the molar ratio of the N-thiocarboxylic anhydride containing a bromophenyl group to the initiator is (10-100):1.

[0052] When the molar ratio of the N-thiocarboxylic anhydride containing a bromophenyl group to the initiator is within the above range, the N-thiocarboxylic anhydride containing a bromophenyl group can fully undergo a ring-opening polymerization reaction under the action of the initiator, exhibiting better polymerization controllability, thereby obtaining a high-yield polypeptide containing a bromophenyl group on the side.

[0053] Illustratively, the molar ratio of the bromophenyl group-containing N-thiocarboxylic anhydride to the initiator may be any one of 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1 and 100:1, or a range consisting of any two of these.

[0054] In a specific embodiment, the inorganic base is one of potassium phosphate and cesium carbonate, the palladium catalyst is one of tris(dibenzylideneacetone)dipalladium and palladium acetate, and the ligand is one of 2-(dicyclohexylphosphino)biphenyl and 2-(di-tert-butylphosphino)biphenyl;

[0055] The molar ratio of the bromophenyl group, aromatic amine derivative, inorganic base, palladium catalyst and ligand in the polypeptide containing bromophenyl group on the side group is 1: (1-2): (2-4): (0.1-0.2): (0.4-0.6).

[0056] When the molar ratio of the bromophenyl group, aromatic amine derivative, inorganic base, palladium catalyst and ligand in the polypeptide with bromophenyl group in the side group is within the above range, the raw material system of the polypeptide with bromophenyl group in the side group and the aromatic amine derivative can fully undergo amination coupling reaction, which is beneficial to prepare the polypeptide with functionalized diphenylamine group in the side group with high yield.

[0057] Illustratively, the molar ratio of the bromophenyl group, aromatic amine derivative, inorganic base, palladium-based catalyst and ligand in the polypeptide having a bromophenyl group-containing side group can be any one of 1:1:2:0.1:0.4, 1:2:4:0.2:0.6, 1:1:4:0.2:0.6, 1:1.5:3:0.1:0.5, 1:2:2:0.1:0.4, 1:1.5:3:0.1:0.5 and 1:1.5:2.5:0.1:0.5, and a range consisting of any five of them.

[0058] In a specific embodiment, the reaction temperature of the amination coupling reaction is 90° C. to 120° C., and the reaction time is 12 h to 36 h.

[0059] When the reaction temperature and reaction time parameters of the amination coupling reaction are within the above range, the activity and rate of the amination coupling reaction can be guaranteed, the occurrence of side reactions can be reduced, and at the same time, a high yield of side-group functionalized diphenylamine-containing peptides can be obtained.

[0060] For example, the reaction temperature for the amination coupling reaction may be any one of 90°C, 100°C, 110°C and 120°C, and a range consisting of any two thereof;

[0061] The reaction time may be any one of 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 24 h, 26 h, 28 h, 30 h, 32 h, 34 h and 36 h, or a range consisting of any two of these.

[0062] In a specific embodiment, the reaction temperature for the ring-opening polymerization reaction is 50° C. to 80° C., and the reaction time is 24 h to 96 h.

[0063] When the reaction temperature and reaction time parameters of the ring-opening polymerization reaction are within the above range, the activity and rate of the ring-opening polymerization reaction can be guaranteed, the occurrence of side reactions can be reduced, and at the same time, a high yield of side-group bromophenyl-containing polymerized peptides can be obtained.

[0064] For example, the reaction temperature for the amination coupling reaction may be any one of 50°C, 55°C, 60°C, 65°C, 70°C, 75°C and 80°C, and a range consisting of any two thereof;

[0065] The reaction time can be any one of 24 h, 30 h, 34 h, 40 h, 44 h, 50 h, 54 h, 60 h, 64 h, 70 h, 74 h, 80 h, 84 h, 90 h and 96 h, or a range consisting of any two of them.

[0066] In a specific embodiment, the N-thiocarboxylic acid anhydride containing a bromophenyl group is one of N-4-bromophenylmethylglycine-N-thiocarboxylic acid anhydride and N-4-bromophenylethylglycine-N-thiocarboxylic acid anhydride; the structural formula of the N-4-bromophenylmethylglycine-N-thiocarboxylic acid anhydride is shown in formula (II), and the structural formula of the N-4-bromophenylethylglycine-N-thiocarboxylic acid anhydride is shown in formula (III):

[0067]

[0068] In the present invention, the specific method for synthesizing N-4-bromophenylmethylglycine-N-thiocarboxylic acid anhydride or N-4-bromophenylethylglycine-N-thiocarboxylic acid anhydride is not particularly limited, as long as the above structure is satisfied.

[0069] In a specific embodiment, the structural formula of the aromatic amine derivative is any one of formula (IV), formula (V), and formula (VI):

[0070]

[0071] Among them, R3 is a hydrogen atom, an alkyl group, an alkoxy group or a phenyl group; R4 to R6 are independently selected from one of a hydrogen atom, an alkyl group, an alkoxy group or a phenyl group; R7 is a hydrogen atom, an alkyl group, an alkoxy group, a sulfonic acid group or a dimethylamino group.

[0072] The present invention uses the aromatic amine derivative of the structural formula to undergo an amination coupling reaction with a polypeptide containing a bromophenyl group on the side group, thereby obtaining a polypeptide containing a functionalized diphenylamine group on the side group with a high yield.

[0073] In a specific embodiment, the specific steps of performing the ring-opening polymerization reaction are: dissolving the N-thiocarboxylic anhydride containing a bromophenyl group in a first organic solvent to obtain a mixed solution, and then adding an initiator to the mixed solution, so that the N-thiocarboxylic anhydride containing a bromophenyl group undergoes a ring-opening polymerization reaction under the action of the initiator to obtain a polypeptide containing a bromophenyl group on the side group, or dissolving the N-thiocarboxylic anhydride containing a bromophenyl group and an initiator in a first organic solvent, so that the N-thiocarboxylic anhydride containing a bromophenyl group undergoes a ring-opening polymerization reaction under the action of the initiator to obtain a polypeptide containing a bromophenyl group on the side group;

[0074] The initiator is one of n-hexylamine, benzylamine, neopentylamine, and methoxy polyethylene glycol amine;

[0075] The first organic solvent is at least one of tetrahydrofuran, dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, tetramethylurea, acetonitrile, benzonitrile, toluene and chloroform.

[0076] In a specific embodiment, the specific steps of the amination coupling reaction are: dissolving the polypeptide containing bromophenyl groups on the side groups, aromatic amine derivatives, inorganic bases, palladium catalysts and ligands in a second organic solvent, and in the presence of inorganic bases, palladium catalysts and ligands, subjecting the raw material system including the polypeptide containing bromophenyl groups on the side groups and aromatic amine derivatives to an amination coupling reaction to obtain the polypeptide containing functionalized diphenylamine groups on the side groups;

[0077] The second organic solvent includes N,N-dimethylformamide.

[0078] The present invention does not particularly limit the specific inert gas atmosphere for the amination coupling reaction, and it can be selected as needed. In some embodiments, the amination coupling reaction can be carried out under a nitrogen atmosphere.

[0079] In some embodiments, the obtained peptide clusters containing bromophenyl groups on the side groups are subjected to a first sedimentation, a first separation and a first drying treatment in sequence, which is beneficial for obtaining a high yield of peptide clusters containing bromophenyl groups on the side groups.

[0080] In some embodiments, the obtained peptides having functionalized diphenylamine groups on the side groups are subjected to a second sedimentation, a second separation and a second drying treatment in sequence, which is beneficial for obtaining a high yield of peptides having functionalized diphenylamine groups on the side groups.

[0081] The second aspect of the present invention provides a peptide having a functionalized diphenylamine group as a side chain, which is prepared by the method for preparing the peptide having a functionalized diphenylamine group as a side chain. The synthetic route for preparing the peptide having a functionalized biphenyl group as a side chain is simple, the raw materials are easy to obtain, the cost is low, and the yield is high. The structure and performance of the peptide having a functionalized biphenyl group as a side chain are easy to control, and can be adjusted by the functional groups on the aromatic amine derivatives.

[0082] The present invention is further described below through specific embodiments.

[0083] The structure of the obtained peptide clusters was determined by 1 H NMR method was used on a Bruker AVANCEⅢ400 superconducting nuclear magnetic resonance instrument, with deuterated dimethyl sulfoxide (DMSO-d6) as the solvent, tetramethylsilane (TMS) as the internal standard, and the test temperature at 20°C. The degree of polymerization was calculated by the integral ratio of the initiator group signal and the peptide backbone signal. The relative molecular weight and molecular weight distribution of the polymer were determined by an Agilent PL-50 gel permeation chromatograph, with DMF containing 0.02 mol / L LiBr as the mobile phase, the flow rate was 1.0 mL / min, the column temperature was 50°C, and monodisperse polystyrene was used as the standard sample.

[0084] The N-4-bromophenylmethylglycine-N-thiocarboxylic anhydride and N-4-bromophenylethylglycine-N-thiocarboxylic anhydride used in the following examples were synthesized according to the method in the reference (European Polymer Journal, 2018, 109, 26-42; Acta Polym. Sin. 2022, 53 12, 1475-1483).

[0085] Example 1

[0086] This embodiment provides a method for preparing a peptide having a functionalized diphenylamine group as a side group represented by formula (VII):

[0087]

[0088] (1) Add 0.42 g (1.47 mmol) of N-4-bromophenylmethylglycine-N-thiocarboxylic anhydride to the reaction flask and add 3.0 mL N,N-dimethylacetamide was used to dissolve the mixture to obtain a solution; then 1.72 mL of a neopentylamine solution (a solution prepared by mixing neopentylamine with N,N-dimethylacetamide (0.0852 mmol / mL, 0.147 mmol)) was added to the solution to obtain a reaction system 1, wherein the molar ratio of N-4-bromophenylmethylglycine-N-thiocarboxylic acid anhydride to neopentylamine in the reaction system 1 was 10:1; the reaction system 1 was reacted at 60° C. for 48 h to obtain a reaction product 1; the reaction product 1 was precipitated with ether three times, separated after centrifugation, and a precipitate 1 was obtained; the precipitate 1 was dried in a vacuum drying oven at a temperature of 40° C. to a constant weight to obtain a white solid (0.334 g, yield 97%), namely poly(N-4-bromophenylmethylglycine); the degree of polymerization of the poly(N-4-bromophenylmethylglycine) was measured to be 10, and the number average molecular weight was 2.35 kg / mol. The number average molecular weight of poly(N-4-bromophenylmethylglycine) was measured by gel permeation chromatography to be 3.2 kg / mol, and the molecular weight distribution was 1.04.

[0089] (2) 96.0 mg (0.041 mmol, containing 0.41 mmol of bromophenyl group) of the white solid obtained in step (1) was placed in a Shrek bottle filled with nitrogen, and aniline (38.2 mg, 0.41 mmol), potassium phosphate (348.1 mg, 1.64 mmol), tris(dibenzylideneacetone)dipalladium (75.1 mg, 0.082 mmol) and 2-(dicyclohexylphosphino)biphenyl (86.2 mg, 0.246 mmol) were added in sequence to obtain a reactant in which the molar ratio of bromophenyl group to aniline, potassium phosphate, tris(dibenzylideneacetone)dipalladium and 2-(dicyclohexylphosphino)biphenyl was 1:1:4:0.2:0.6; then 3.5 mL of 4-nitropropene was added. The reactants were dissolved in N,N-dimethylformamide to obtain reaction system 2, and reaction system 2 was reacted at 100° C. for 24 h to obtain reaction product 2; reaction product 2 was centrifuged to remove impurities, and then precipitated three times in a methanol / ether (volume ratio 1:4) mixed solvent, centrifuged and separated to obtain precipitate 2; precipitate 2 was dried in a vacuum drying oven at a temperature of 40° C. to constant weight to obtain a light brown solid (86.9 mg, yield 86%), which is the poly-peptide (α1-poly-peptide) with a functionalized diphenylamine group on the side group shown in (VII), and its H NMR spectrum is as follows: Figure 1 The number average molecular weight measured by gel permeation chromatography is 7.1 kg / mol, and the molecular weight distribution is 1.13.

[0090] Example 2

[0091] This embodiment provides a method for preparing a peptide having a functionalized diphenylamine group as a side group represented by formula (VIII):

[0092]

[0093] The experimental procedure (1) is the same as that in Example 1.

[0094] (2) 95.8 mg (0.041 mmol, containing 0.41 mmol of bromophenyl group) of the white solid obtained in step (1) was placed in a Shrek bottle filled with nitrogen, and 4-methoxyaniline (75.7 mg, 0.615 mmol), cesium carbonate (400.7 mg, 1.23 mmol), tris(dibenzylideneacetone)dipalladium (37.5 mg, 0.041 mmol) and 2-(dicyclohexylphosphino)biphenyl (71.9 mg, 0.205 mmol) were added in sequence to obtain a reactant, in which the molar ratio of the bromophenyl group to 4-methoxyaniline, cesium carbonate, tris(dibenzylideneacetone)dipalladium and 2-(dicyclohexylphosphino)biphenyl was 1:1.5:3:0.1:0.5; then 3.5 mL of 4-methoxyaniline was added. The reactants were dissolved in N,N-dimethylformamide to obtain reaction system 2, and reaction system 2 was reacted at 110° C. for 24 h to obtain reaction product 2; reaction product 2 was centrifuged to remove impurities, and then precipitated three times in a methanol / ether (volume ratio 1:4) mixed solvent, centrifuged and separated to obtain precipitate 2; precipitate 2 was dried in a vacuum drying oven at a temperature of 40° C. to constant weight to obtain a light brown solid (124.5 mg, yield 90%), which is the side group of the functionalized diphenylamine group-containing peptide (α2-peptide) shown in (VIII), and its nuclear magnetic hydrogen spectrum is as follows Figure 2 The number average molecular weight measured by gel permeation chromatography is 7.9 kg / mol, and the molecular weight distribution is 1.06.

[0095] Example 3

[0096] This embodiment provides a method for preparing a peptide having a functionalized diphenylamine group as a side group represented by formula (IX):

[0097]

[0098] The experimental procedure (1) is the same as that in Example 1.

[0099] (2) 95.9 mg (0.041 mmol, containing 0.41 mmol of bromophenyl group) of the white solid obtained in step (1) was placed in a Shrek bottle filled with nitrogen, and 1-(4-aminophenyl)-1,2,2-triphenylethylene (284.9 mg, 0.82 mmol), potassium phosphate (174.0 mg, 0.82 mmol), palladium acetate (9.2 mg, 0.041 mmol) and 2-(dicyclohexylphosphino)biphenyl (57.5 mg, 0.164 mmol) were added in sequence to obtain a reactant in which the molar ratio of the bromophenyl group to 1-(4-aminophenyl)-1,2,2-triphenylethylene, potassium phosphate, palladium acetate and 2-(dicyclohexylphosphino)biphenyl was 1:2:2:0.1:0.4; then 3.5 mL of 4-nitropropene was added. The reactants were dissolved in N,N-dimethylformamide to obtain reaction system 2, and reaction system 2 was reacted at 120° C. for 12 h to obtain reaction product 2; reaction product 2 was centrifuged to remove impurities, and then precipitated three times in a methanol / ether (volume ratio 1:4) mixed solvent, centrifuged and separated to obtain precipitate 2; precipitate 2 was dried in a vacuum drying oven at a temperature of 40° C. to constant weight to obtain a light brown solid (302.4 mg, yield 87%), which is the poly-peptide (α3-poly-peptide) with a functionalized diphenylamine group on the side group shown in (IX), and its H NMR spectrum is as follows: Figure 3 The number average molecular weight measured by gel permeation chromatography is 8.5 kg / mol, and the molecular weight distribution is 1.10.

[0100] The α3-peptide was dissolved in a tetrahydrofuran / water mixed solution and fluorescence spectroscopy was performed. Figure 4 This is the fluorescence spectrum of α3-peptide in tetrahydrofuran / water mixed solution.

[0101] Depend on Figure 4 It can be seen that when excited by 415nm light, the α3-clustered peptide showed a fluorescence emission peak at 528nm, proving that the preparation method provided by the present invention can successfully prepare a clustered peptide with a side group containing a functionalized diphenylamine group and having an aggregation-induced emission effect, indicating that the clustered peptide with a side group containing a functionalized diphenylamine group provided by the present invention can be applied to the field of fluorescence.

[0102] Example 4

[0103] This embodiment provides a method for preparing a peptide having a functionalized diphenylamine group as a side group represented by formula (X):

[0104]

[0105] The experimental procedure (1) is the same as that in Example 1.

[0106] (2) 95.5 mg (0.041 mmol, containing 0.41 mmol of bromophenyl group) of the white solid obtained in step (1) was placed in a Shrek bottle filled with nitrogen, and 4-amino-4'-sulfonic acid azobenzene (170.5 mg, 0.615 mmol), potassium phosphate (261.2 mg, 1.23 mmol), tris(dibenzylideneacetone)dipalladium (37.6 mg, 0.041 mmol) and 2-(di-tert-butylphosphine)biphenyl (61.2 mg, 0.205 mmol) were added in sequence to obtain a reactant in which the molar ratio of the bromophenyl group to 4-amino-4'-sulfonic acid azobenzene, potassium phosphate, tris(dibenzylideneacetone)dipalladium and 2-(di-tert-butylphosphine)biphenyl was 1:1.5:3:0.1:0.5; then 3.5 mL of 4-amino-4'-sulfonic acid azobenzene, potassium phosphate, tris(dibenzylideneacetone)dipalladium and 2-(di-tert-butylphosphine)biphenyl were added. The reactants were dissolved in N,N-dimethylformamide to obtain reaction system 2, and reaction system 2 was reacted at 100° C. for 24 h to obtain reaction product 2; reaction product 2 was centrifuged to remove impurities, and then precipitated three times in a methanol / ether (volume ratio 1:4) mixed solvent, centrifuged and separated to obtain precipitate 2; precipitate 2 was dried in a vacuum drying oven at a temperature of 40° C. to constant weight to obtain a yellow solid (197.9 mg, yield 85%), which is the poly-peptide (α4-poly-peptide) with a functionalized diphenylamine group on the side group shown in (X), and its H NMR spectrum is as follows: Figure 5 The number average molecular weight measured by gel permeation chromatography is 10.9 kg / mol, and the molecular weight distribution is 1.14.

[0107] Figure 6 is the UV-visible absorption spectrum of α4-peptide under different wavelength conditions: Figure 6 a is under the condition of light with wavelength of 450nm; Figure 6 b is under the condition of light illumination of 530nm wavelength.

[0108] from Figure 6 The characteristic absorption peak of α4-peptide was observed at about 425nm, which corresponds to the absorption peak of the trans configuration of the azobenzene group. Since the azobenzene ring is connected to an amino group, the strong electron-donating effect of the amino group will cause the absorption band generated by the π-π* transition to red-shift, overlapping with the absorption band generated by the n-π* transition. Figure 6 As shown in a, when the α4-peptide was irradiated by 450nm blue light, the absorption peak at 425nm continued to decrease until it reached a steady state after 60s, and the azobenzene in the α4-peptide gradually changed from the trans configuration to the cis configuration; Figure 6As shown in b, under the irradiation of 530nm green light, the absorption peak of α4-clustered peptide was observed to rise continuously at 425nm. After 60s of continuous irradiation, the cis configuration recovered to the more stable trans configuration, proving that the preparation method provided by the present invention can successfully prepare the clustered peptide with functionalized diphenylamine group in the side group and light responsiveness, indicating that the clustered peptide with functionalized diphenylamine group in the side group provided by the present invention can be applied to the field of intelligent response.

[0109] Example 5

[0110] This embodiment provides a method for preparing a peptide having a functionalized diphenylamine group as a side group represented by formula (XI):

[0111]

[0112] (1) Add 0.45 g (1.50 mmol) of N-4-bromophenylethylglycine-N-thiocarboxylic anhydride to the reaction flask and add 3.0 mL N,N-dimethylformamide was used to dissolve the mixture to obtain a solution; then 0.82 mL of n-hexylamine solution (a solution prepared by configuring n-hexylamine and N,N-dimethylacetamide (0.0912 mmol / mL, 0.075 mmol)) was added to the solution to obtain a reaction system 1, in which the molar ratio of N-4-bromophenylethylglycine-N-thiocarboxylic acid anhydride to n-hexylamine was 20:1; the reaction system 1 was reacted at 70°C for 72 hours to obtain a reaction product 1; the reaction product 1 was precipitated with ether three times, separated after centrifugation, and a precipitate 1 was obtained; the precipitate 1 was dried in a vacuum drying oven at a temperature of 40°C to a constant weight to obtain a white solid (0.341 g, yield 93%), which was poly(N-4-bromophenylethylglycine); the degree of polymerization of the poly(N-4-bromophenylethylglycine) was measured to be 18, and the number average molecular weight was 4.42 kg / mol. The number average molecular weight of poly(N-4-bromophenylethylglycine) measured by gel permeation chromatography was 7.1 kg / mol, and the molecular weight distribution was 1.08.

[0113] (2) 120.0 mg (0.0271 mmol, containing 0.488 mmol of bromophenyl group) of the white solid obtained in step (1) was placed in a Shrek bottle filled with nitrogen, and 4-amino-4'-dimethylaminoazobenzene (175.9 mg, 0.732 mmol), potassium phosphate (310.0 mg, 1.46 mmol), tris(dibenzylideneacetone)dipalladium (44.7 mg, 0.0488 mmol) and 2-(dicyclohexylphosphino)biphenyl (85.5 mg, 0.244 mmol) were added in sequence to obtain a reactant in which the molar ratio of the bromophenyl group to 4-amino-4'-dimethylaminoazobenzene, potassium phosphate, tris(dibenzylideneacetone)dipalladium and 2-(dicyclohexylphosphino)biphenyl was 1:1.5:3:0.1:0.5; then 4 mL of 4% ethyl acetate was added. The reactants were dissolved in N,N-dimethylformamide to obtain reaction system 2, and reaction system 2 was reacted at 90°C for 36 hours to obtain reaction product 2; reaction product 2 was centrifuged to remove impurities, and then precipitated three times in a methanol / ether (volume ratio 1:4) mixed solvent, centrifuged and separated to obtain precipitate 2; precipitate 2 was dried in a vacuum drying oven at a temperature of 40°C to constant weight to obtain a yellow solid (228.2 mg, yield 89%), which is the poly-peptide (α5-poly-peptide) with a functionalized diphenylamine group on the side group shown in (XI), and its H NMR spectrum is as follows Figure 7 The number average molecular weight measured by gel permeation chromatography is 20.5 kg / mol, and the molecular weight distribution is 1.21.

[0114] Example 6

[0115] This embodiment provides a method for preparing a peptide having a functionalized diphenylamine group as a side group represented by formula (XII):

[0116]

[0117] (1) Add 0.45 g (1.50 mmol) of N-4-bromophenylethylglycine-N-thiocarboxylic anhydride and 0.113 g (0.15 mmol) of methoxypolyethylene glycol amine (mPEG) with a number average molecular weight of 750 into a reaction flask. 15 -NH2) (CAS No. 80506-64-5) to obtain a mixture, 3.0 mL of N,N-dimethylformamide was added to dissolve the mixture to obtain reaction system 1, in which N-4-bromophenylethylglycine-N-thiocarboxylic acid anhydride and mPEG 15The molar ratio of -NH2 is 10:1, and the reaction system 1 is reacted at 50°C for 96 hours to obtain a reaction product 1; the reaction product 1 is precipitated with ether three times, separated after centrifugation, and a precipitate 1 is obtained; the precipitate 1 is dried in a vacuum drying oven at a temperature of 40°C to constant weight to obtain a white solid (0.449 g, yield 95%), which is polyethylene glycol-b-poly (N-4-bromophenylethylglycine) A. The degree of polymerization of the poly (N-4-bromophenylethylglycine) block is measured to be 10, and the number average molecular weight of polyethylene glycol-b-poly (N-4-bromophenylethylglycine) is 3.15 kg / mol. The number average molecular weight of polyethylene glycol-b-poly (N-4-bromophenylethylglycine) is 7.6 kg / mol and the molecular weight distribution is 1.07 by gel permeation chromatography.

[0118] (2) 119.7 mg (0.038 mmol, containing 0.38 mmol of bromophenyl group) of the white solid obtained in step (1) was placed in a Shrek bottle filled with nitrogen, and 4-aminoazobenzene (112.4 mg, 0.57 mmol), potassium phosphate (201.7 mg, 0.95 mmol), tris(dibenzylideneacetone)dipalladium (34.8 mg, 0.038 mmol) and 2-(dicyclohexylphosphino)biphenyl (66.6 mg, 0.19 mmol) were added in sequence to obtain a reactant in which the molar ratio of the bromophenyl group to 4-aminoazobenzene, potassium phosphate, tris(dibenzylideneacetone)dipalladium and 2-(dicyclohexylphosphino)biphenyl was 1:1.5:2.5:0.1:0.5; then 4 mL of 4% bromine was added. The reactants were dissolved in N,N-dimethylformamide to obtain reaction system 2, and reaction system 2 was reacted at 100°C for 24 hours to obtain reaction product 2; reaction product 2 was centrifuged to remove impurities, and then precipitated with ether three times, separated after centrifugation, to obtain precipitate 2; precipitate 2 was dried in a vacuum drying oven at a temperature of 40°C to constant weight to obtain a yellow solid (173.2 mg, yield 86%), which is the side group of the functionalized diphenylamine group-containing peptide (α6-peptide) shown in (XII), and its nuclear magnetic hydrogen spectrum is as follows Figure 8 The number average molecular weight measured by gel permeation chromatography is 14.6 kg / mol, and the molecular weight distribution is 1.22.

[0119] Example 7

[0120] This embodiment provides a method for preparing a peptide having a functionalized diphenylamine group as a side group represented by formula (XIII):

[0121]

[0122] (1) Add 0.30 g (1.00 mmol) of N-4-bromophenylethylglycine-N-thiocarboxylic anhydride and 0.201 g (0.10 mmol) of methoxypolyethylene glycol amine (mPEG) with a number average molecular weight of 2000 into a reaction flask. 44 -NH2) (CAS No. 80506-64-5) to obtain a mixture, 4.0 mL of N-methylpyrrolidone was added to dissolve the mixture to obtain a reaction system 1, in which N-4-bromophenylethylglycine-N-thiocarboxylic acid anhydride and mPEG 44 The molar ratio of -NH2 is 10:1, and the reaction system 1 is reacted at 80°C for 48h to obtain a reaction product 1; the reaction product 1 is precipitated with ether three times, separated after centrifugation, and a precipitate 1 is obtained; the precipitate 1 is dried in a vacuum drying oven at a temperature of 40°C to constant weight to obtain a white solid (0.406g, yield 92%), which is polyethylene glycol-b-poly(N-4-bromophenylethylglycine) B. The degree of polymerization of the poly(N-4-bromophenylethylglycine) block is measured to be 8, and the number average molecular weight of polyethylene glycol-b-poly(N-4-bromophenylethylglycine) is 3.92kg / mol. The number average molecular weight of polyethylene glycol-b-poly(N-4-bromophenylethylglycine) is 13.5kg / mol and the molecular weight distribution is 1.04 as measured by gel permeation chromatography.

[0123] (2) 141.1 mg (0.036 mmol, containing 0.288 mmol of bromophenyl group) of the white solid obtained in step (1) was placed in a Shrek bottle filled with nitrogen, and 1-(4-aminophenyl)-1,2,2-triphenylethylene (150.1 mg, 0.432 mmol), potassium phosphate (183.4 mg, 0.864 mmol), tris(dibenzylideneacetone)dipalladium (26.4 mg, 0.0288 mmol) and 2-(dicyclohexylphosphino)biphenyl (50.5 mg, 0.144 mmol) were added in sequence to obtain a reactant in which the molar ratio of the bromophenyl group to 1-(4-aminophenyl)-1,2,2-triphenylethylene, potassium phosphate, tris(dibenzylideneacetone)dipalladium and 2-(dicyclohexylphosphino)biphenyl was 1:1.5:3:0.1:0.5; then 4 mL of 4% ethyl acetate was added. The reactants were dissolved in N,N-dimethylformamide to obtain reaction system 2, and reaction system 2 was reacted at 100°C for 24 hours to obtain reaction product 2; reaction product 2 was centrifuged to remove impurities, and then precipitated with ether three times, separated after centrifugation, to obtain precipitate 2; precipitate 2 was dried in a vacuum drying oven at a temperature of 40°C to constant weight to obtain a light brown solid (225.0 mg, yield 84%), which is the poly-peptide (α7-poly-peptide) with a functionalized diphenylamine group on the side group shown in (XIII), and its H NMR spectrum is as follows Fig. 9The number average molecular weight measured by gel permeation chromatography is 22.8 kg / mol, and the molecular weight distribution is 1.26.

[0124] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a peptide having a functionalized diphenylamine group as a side group, characterized in that: include: N-thiocarboxylic anhydride containing bromophenyl groups undergoes a ring-opening polymerization reaction under the action of an initiator to obtain a polypeptide containing bromophenyl groups on the side groups; In the presence of an inorganic base, a palladium catalyst and a ligand, a raw material system including the polypeptide containing a bromophenyl group on the side group and an aromatic amine derivative undergoes an amination coupling reaction to obtain a polypeptide containing a functionalized diphenylamine group on the side group. The polypeptide containing a functionalized diphenylamine group on the side group has a structural formula as shown in formula (I): Among them, R1 is any one of n-hexyl, benzyl, neopentyl, and methoxypolyethylene glycol; R2 is any one of hydrogen atom, alkyl, alkoxy, phenyl, triphenylvinyl, and diazenephenyl; n is an integer between 10 and 100; and x is 1 or 2.

2. The method for preparing a peptide having a functionalized diphenylamine group as a side group according to claim 1, characterized in that: The molar ratio of the N-thiocarboxylic anhydride containing a bromophenyl group to the initiator is (10-100):

1.

3. The method for preparing a peptide having a functionalized diphenylamine group as a side group according to claim 1, characterized in that: The inorganic base is one of potassium phosphate and cesium carbonate, the palladium catalyst is one of tris(dibenzylideneacetone)dipalladium and palladium acetate, and the ligand is one of 2-(dicyclohexylphosphino)biphenyl and 2-(di-tert-butylphosphino)biphenyl; The molar ratio of the bromophenyl group, aromatic amine derivative, inorganic base, palladium catalyst and ligand in the polypeptide containing bromophenyl group on the side group is 1: (1-2): (2-4): (0.1-0.2): (0.4-0.6).

4. The method for preparing a peptide having a functionalized diphenylamine group as a side group according to claim 1, characterized in that: The reaction temperature of the amination coupling reaction is 90° C. to 120° C., and the reaction time is 12 h to 36 h.

5. The method for preparing a peptide having a functionalized diphenylamine group as a side group according to claim 1, characterized in that: The reaction temperature for the ring-opening polymerization reaction is 50° C. to 80° C., and the reaction time is 24 h to 96 h.

6. The method for preparing a peptide having a functionalized diphenylamine group as a side group according to claim 1, characterized in that: The N-thiocarboxylic acid anhydride containing a bromophenyl group is one of N-4-bromophenylmethylglycine-N-thiocarboxylic acid anhydride and N-4-bromophenylethylglycine-N-thiocarboxylic acid anhydride; the structural formula of the N-4-bromophenylmethylglycine-N-thiocarboxylic acid anhydride is shown in formula (II), and the structural formula of the N-4-bromophenylethylglycine-N-thiocarboxylic acid anhydride is shown in formula (III):

7. The method for preparing a peptide having a functionalized diphenylamine group as a side group according to claim 1, characterized in that: The structural formula of the aromatic amine derivative is any one of formula (IV), formula (V) and formula (VI): Among them, R3 is a hydrogen atom, an alkyl group, an alkoxy group or a phenyl group; R4 to R6 are independently selected from one of a hydrogen atom, an alkyl group, an alkoxy group or a phenyl group; R7 is a hydrogen atom, an alkyl group, an alkoxy group, a sulfonic acid group or a dimethylamino group.

8. The method for preparing a peptide having a functionalized diphenylamine group as a side group according to claim 1, characterized in that: The specific steps of the ring-opening polymerization reaction are: dissolving the N-thiocarboxylic anhydride containing bromophenyl groups in a first organic solvent to obtain a mixed solution, and then adding an initiator to the mixed solution, so that the N-thiocarboxylic anhydride containing bromophenyl groups undergoes a ring-opening polymerization reaction under the action of the initiator to obtain a polypeptide containing bromophenyl groups on the side groups, or dissolving the N-thiocarboxylic anhydride containing bromophenyl groups and the initiator in a first organic solvent, so that the N-thiocarboxylic anhydride containing bromophenyl groups undergoes a ring-opening polymerization reaction under the action of the initiator to obtain a polypeptide containing bromophenyl groups on the side groups; The initiator is one of n-hexylamine, benzylamine, neopentylamine, and methoxy polyethylene glycol amine; The first organic solvent is at least one of tetrahydrofuran, dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, tetramethylurea, acetonitrile, benzonitrile, toluene and chloroform.

9. The method for preparing a peptide having a functionalized diphenylamine group as a side group according to claim 1, characterized in that: The specific steps of the amination coupling reaction are: dissolving the polypeptide containing bromophenyl groups on the side groups, aromatic amine derivatives, inorganic bases, palladium catalysts and ligands in a second organic solvent, and in the presence of inorganic bases, palladium catalysts and ligands, subjecting the raw material system including the polypeptide containing bromophenyl groups on the side groups and aromatic amine derivatives to an amination coupling reaction to obtain the polypeptide containing functionalized diphenylamine groups on the side groups; The second organic solvent includes N,N-dimethylformamide.

10. A peptide having a functionalized diphenylamine group as a side group, characterized in that: The peptide is prepared by the method for preparing a polymeric peptide having a side group containing a functionalized diphenylamine group as described in any one of claims 1 to 9.

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