CN110128502B - Amphiphilic polypeptide molecule with temperature-sensitive aggregation-induced emission characteristic and preparation method thereof - Google Patents
Amphiphilic polypeptide molecule with temperature-sensitive aggregation-induced emission characteristic and preparation method thereof Download PDFInfo
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 40
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 33
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 32
- 230000002776 aggregation Effects 0.000 title claims abstract description 27
- 238000004220 aggregation Methods 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title abstract description 5
- 239000000243 solution Substances 0.000 claims abstract description 28
- 239000007864 aqueous solution Substances 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 5
- 239000004005 microsphere Substances 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 238000003756 stirring Methods 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 9
- 238000001704 evaporation Methods 0.000 claims description 9
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 9
- 239000012074 organic phase Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 229940125904 compound 1 Drugs 0.000 claims description 5
- 238000010898 silica gel chromatography Methods 0.000 claims description 5
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 4
- 229940125782 compound 2 Drugs 0.000 claims description 4
- 229940125898 compound 5 Drugs 0.000 claims description 4
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 claims description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012295 chemical reaction liquid Substances 0.000 claims description 3
- 229940126214 compound 3 Drugs 0.000 claims description 3
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 claims description 3
- 241001274216 Naso Species 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims 1
- 235000019341 magnesium sulphate Nutrition 0.000 claims 1
- -1 alkoxy ether Chemical compound 0.000 abstract description 13
- 102000008186 Collagen Human genes 0.000 abstract description 12
- 108010035532 Collagen Proteins 0.000 abstract description 12
- 229920001436 collagen Polymers 0.000 abstract description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 12
- 230000008859 change Effects 0.000 abstract description 8
- JLZUZNKTTIRERF-UHFFFAOYSA-N tetraphenylethylene Chemical group C1=CC=CC=C1C(C=1C=CC=CC=1)=C(C=1C=CC=CC=1)C1=CC=CC=C1 JLZUZNKTTIRERF-UHFFFAOYSA-N 0.000 abstract description 6
- 239000012620 biological material Substances 0.000 abstract description 4
- 238000004020 luminiscence type Methods 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 abstract description 2
- 238000001338 self-assembly Methods 0.000 abstract 1
- 229920002554 vinyl polymer Polymers 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 239000012071 phase Substances 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 230000007704 transition Effects 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000002390 rotary evaporation Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 108010039918 Polylysine Proteins 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000000295 emission spectrum Methods 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229920000656 polylysine Polymers 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 101000933967 Pseudomonas phage KPP25 Major capsid protein Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000004703 alkoxides Chemical group 0.000 description 1
- 238000000089 atomic force micrograph Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
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- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1007—Non-condensed systems
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- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
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Abstract
The invention relates to an amphiphilic polypeptide molecule with temperature-sensitive aggregation-induced emission characteristics and a preparation method thereof. The structural formula of the amphiphilic polypeptide molecule is as follows:
where x=ome or OEt, n=1 or 2. The amphiphilic polypeptide molecule with the temperature-sensitive aggregation-induced emission characteristic disclosed by the invention is introduced with the temperature-sensitive characteristic through a first generation alkoxy ether primitive, is introduced with chiral characteristics through collagen model peptide sequence peptide, and is introduced with the hydrophobicity and aggregation-induced emission characteristic through tetraphenyl ethylene part. The aggregation degree of the molecule in the aqueous solution can be controlled through the phase change process guided by the alkoxy ether dendron, and the fluorescence characteristic of the solution is further controlled by utilizing the aggregation-induced luminescence property of the tetraphenyl vinyl element. In addition, since the structure has amphiphilic properties, it can form nano-microspheres by self-assembly in aqueous solution. The amphiphilic polypeptide molecule has potential application in the fields of intelligent biological materials, photoelectric element miniaturization, thermoluminescent materials and the like.
Description
Technical Field
The invention relates to the field of biological materials and fluorescent materials, in particular to an amphiphilic polypeptide molecule with temperature-sensitive aggregation-induced emission characteristics and a preparation method thereof.
Background
Collagen is a major structural protein in animals, accounting for about one third of the total protein content in humans. Although the collagen content is very high in the nature, the size is huge, the pathogenicity is easy, the post-modification is difficult, and great difficulty is brought to the research of the collagen structure. Therefore, artificial synthesis of collagen sequence structural polypeptides has been attracting attention. The classical sequence of collagen is X-Y-Gly, where the X and Y positions are normally occupied by proline and hydroxyproline, namely proline-hydroxyproline-glycine POG. The invention is characterized by (POG) n The sequence peptide is taken as a main body and is subjected to functional modification at an amino terminal and a carboxyl terminal.
Alkoxy ethers (Oligo (ethylene glycoyl), OEG) are a well known class of biocompatible motifs that are widely used for modification of polypeptide bases. Wherein, the tree-branched OEG motif is connected to the polypeptide, which can increase the hydrophilicity and simultaneously is hopeful to endow the polypeptide with the temperature sensitivity. Zhang Afang et al (Afang Zhang, et al.J. Polym. Sci., Part A: Polym. Chem.2015, 53, 33-41) designs and synthesizes a dynamic linkage alkoxy ether dendronized polylysine, and the side alkoxy ether dendronized element is connected with a main chain through an imine bond. The polylysine has excellent temperature-sensitive property, rapid phase change and small hysteresis, and the phase change temperature can be easily regulated and controlled by changing the proportion of different dendronized elements. In addition, during phase transition, the polypeptide is converted from alpha helix to random coil in conformation, and reversible conformation control can be realized through reversible temperature-sensitive phase transition behavior.
In recent years, tetraphenyl ethylene has been frequently used as a modifying group as a prototype molecule having aggregation-induced emission (AIE). While imparting overall hydrophobicity to the compound, it also imparts the functional characteristics of AIE. But is extremely limited in its application in the field of biology due to its excessive hydrophobicity.
Disclosure of Invention
The invention aims at providing an amphiphilic polypeptide molecule with temperature-sensitive aggregation-induced emission characteristics.
The second object of the present invention is to provide a method for preparing such an amphiphilic polypeptide.
In order to achieve the aim of the invention, the amphiphilic polypeptide molecule takes a generation of dendronized alkoxy ether modified collagen sequence peptide as a hydrophilic element, takes a tetraphenyl ethylene structure as a hydrophobic element, and links the two parts through an amide bond. The temperature sensitive characteristic is introduced through the first generation alkoxy ether element, the chiral characteristic is introduced through the collagen model peptide part, and the hydrophobicity and aggregation-induced luminescence characteristic are introduced through the tetraphenyl ethylene part. The specific reaction equation is:
according to the mechanism, the invention adopts the following technical scheme:
the amphiphilic polypeptide molecule with the temperature-sensitive aggregation-induced emission characteristic is characterized by having a structural formula as follows:
wherein x=ome or OEt, n=1 to 10.
The microsphere size of the amphiphilic polypeptide molecule is 100-500nm.
The method for preparing the amphiphilic polypeptide molecule with the temperature-sensitive aggregation-induced emission characteristic is characterized by comprising the following specific steps of:
a. compound 1 and compound 2 were combined in the order of 1: dissolving 1 mol ratio in a proper amount of dry Dichloromethane (DCM), adding 4-5 equivalents of N, N Diisopropylethylamine (DIPEA) under nitrogen atmosphere and ice bath condition, stirring at 300-500 r/min for 30min, removing ice bath, reacting for 6-12 h, washing the reaction solution with saturated NaCl solution for 1-2 times, extracting the separated solution with DCM, separating the solution with anhydrous MgSO 4 Drying the organic phase, filtering, purifying by silica gel column chromatography, eluting with DCM/MeOH (20:1, v/v), and evaporating the solvent to obtain compound 3;
b. will be 1 time equivalentCompound 3 of (2) is dissolved in an appropriate amount of MeOH/H 2 Adding 15 times equivalent of LiOH H into the mixed solvent of O under the ice bath condition 2 O, stirring at a speed of 300-500 r/min, stirring for 30min, removing the ice bath, reacting for 3-5 h, evaporating the reaction liquid, dissolving with pure water, and then using 10% NaSO 4 The pH of the solution is adjusted to 5-6, and then DCM is used for extracting and separating liquid, and anhydrous MgSO is used 4 Drying the organic phase, filtering, and evaporating the solvent to obtain a compound 4;
c. dissolving one equivalent of compound 4 in a proper amount of dried DCM, respectively adding 1.1 equivalent of pentafluorophenol (PfpOH) and 1.1 equivalent of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC. HCl) under the conditions of nitrogen atmosphere and ice bath, stirring at a speed of 300-500 r/min for 30min, removing the ice bath, reacting for 4-6 h, and then using saturated NaHCO 3 The reaction mixture was washed once with an aqueous solution and a saturated NaCl solution, and after separating the mixture by DCM extraction, the mixture was washed with anhydrous MgSO 4 Drying the organic phase, filtering, purifying by silica gel column chromatography, eluting with DCM/MeOH (30:1, v/v), and evaporating the solvent to obtain compound 5;
d. dissolving a compound 5 and 1- (4-aminobenzene) -1, 2-tristyrene in N, N-Dimethylamide (DMF) according to the molar ratio of 1:1.1, adding 4-10 times equivalent of DIPEA under the nitrogen atmosphere and ice bath condition, stirring at the speed of 300-500 r/min, stirring for 30min, removing the ice bath, reacting for 6-12 h, washing the reaction solution with saturated NaCl solution for 1-2 times, extracting the separated solution with DCM, and then separating the solution with anhydrous MgSO 4 The organic phase was dried and filtered, purified by column chromatography on silica gel eluting with DCM/MeOH (20:1, v/v) and the solvent evaporated to dryness to give the final product compound 6.
The invention takes collagen sequence short peptide as a main body to lay a chiral foundation for the whole molecule. The amino terminal is modified by dendronized alkoxy ether, and a temperature-sensitive mechanism is introduced while the hydrophilicity is increased. The carboxyl terminal is modified by tetraphenyl vinyl unit, and the peptide bond of the collagen sequence modified by alkoxy ether forms an amphiphilic structure, and simultaneously, the functional characteristic of aggregation-induced luminescence is endowed to the whole compound. It is worth mentioning that the temperature-sensitive nature of the dendronized alkoxide ether unit is that when the temperature is raised, alkoxide chains are collapsed and aggregated in a hydrophobic manner, and the aggregation of tetraphenylethylene part of the amphiphilic polypeptide can be indirectly caused, that is, in practice, the amphiphilic polypeptide molecule designed by the invention has a temperature-sensitive aggregation-induced luminescence phenomenon. The amphiphilic polypeptide molecule has potential application in the fields of intelligent biological materials, photoelectric element miniaturization, thermoluminescent materials and the like.
The amphiphilic polypeptide molecule with the temperature-sensitive aggregation-induced emission characteristic has obvious phase transition temperature in the aqueous solution, the passing rate of the aqueous solution is reduced from 90% -100% to 3% -5%, and the phase transition temperature (X=ome or OEt) can be changed by changing the dendronized alkoxy ether end-capping element, so that the phase transition temperature is controllable, and the amphiphilic polypeptide molecule can be applied to the aspects of temperature sensors, intelligent biological materials and the like.
The fluorescence intensity of the amphiphilic polypeptide molecule with the temperature-sensitive aggregation-induced emission characteristic in the tetrahydrofuran-assisted aqueous solution can change along with the change of temperature, has obvious temperature response performance, and can be applied to the fields of photoelectric element miniaturization, thermoluminescent materials and the like.
The invention has the following outstanding characteristics and remarkable advantages:
1. the amphiphilic polypeptide molecule is obtained by linking tetraphenyl ethylene units and collagen sequence peptides modified by dendronized alkoxy ether.
2. The assembly of the amphiphilic macromolecules shows good temperature-sensitive behavior in tetrahydrofuran-assisted aqueous solution, and the phase transition temperature is 26.7 ℃.
3. The series of solutions are found to have aggregation-induced emission phenomenon by changing the water/tetrahydrofuran mixed solvent ratio (20% -80%).
4. The aggregation state of the fluorescent dye in the solution can be changed by changing the temperature, so that the aim of enhancing the fluorescence induced by temperature-sensitive aggregation is fulfilled.
5. In tetrahydrofuran-assisted aqueous solution, amphiphilic polypeptide molecules self-assemble into nano-microspheres of about 300 nm.
Drawings
FIG. 1 shows an amphiphilic polypeptide molecule EtG1-POG-TPE 1 H NMR spectrum.
FIG. 2 is a mass spectrum of EtG 1-POG-TPE.
FIG. 3 is a temperature-sensitive phase transition turbidity graph of EtG 1-POG-TPE.
FIG. 4 is a fluorescence spectrum of EtG1-POG-TPE aggregation-induced fluorescence enhancement.
FIG. 5 is a fluorescence spectrum of EtG1-POG-TPE with enhanced aggregation-induced fluorescence at temperature.
FIG. 6 is an Atomic Force Microscope (AFM) image of EtG 1-POG-TPE.
Detailed Description
Preferred embodiments of the present invention are described in detail below:
embodiment one:
synthesis with EtG1-POG-TPE (x=oet, n=1):
a. adding ethoxy-capped first generation dendron alkoxy ether carboxylic acid active ester into a dried 100mL reaction bottle, adding dichloromethane, stirring and dissolving, adding collagen Peptide (POG) under ice bath condition, stirring and dissolving, adding N, N diisopropylethylamine, replacing nitrogen for three times, maintaining nitrogen atmosphere, removing ice bath after 10min, and continuously stirring at room temperature for reaction for 12h. After the reaction is completed, the solvent is removed by rotary evaporation, and the intermediate product EtG1-POG is obtained by column chromatography purification, and the structure is
；
b. EtG1-POG was put into a dry 100mL flask, dissolved by stirring with an appropriate amount of methanol/water (5:1), liOH was added under ice bath conditions, the ice bath was removed after stirring for 10min, and the reaction was stirred at room temperature for 5h. After the reaction is completed, the methanol is dried by spin, KHSO is added 4 The solution is subjected to pH adjustment to weak acid, extracted by methylene dichloride, dried and filtered, and then the solvent is removed by rotary evaporation to obtain an intermediate product EtG1-POG-COOH,
the structure is that
；
c. EtG1-POG-COOH was dissolved in dry dichloromethane and pentafluorophenol and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC. HCl) were added under ice-bath. The nitrogen was replaced three times and the nitrogen atmosphere was maintained, after 10min the ice bath was removed and the reaction was stirred at room temperature for 8h. Then 1- (4-aminobenzene) -1, 2-tristyrene and N, N diisopropylethylamine are directly added into the reaction liquid under the ice bath condition, nitrogen is replaced for three times, the nitrogen atmosphere is kept, the ice bath is removed after 10min, and the stirring reaction is continued for 12h at room temperature. After the reaction is completed, the solvent is removed by rotary evaporation, the final target product EtG1-POG-TPE is obtained by column chromatography purification, the nuclear magnetic hydrogen spectrum and mass spectrum of the structural characterization are shown in figures 1 and 2,
the structure is that
。
Embodiment two:
EtG1-POG-TPE was dissolved in tetrahydrofuran to a concentration of 0.5mg/mL in water. Because the alkoxy ether has temperature-sensitive behavior, when the alkoxy ether is heated to a certain temperature, the aqueous solution becomes turbid, and the solution returns to a clear state after the temperature is reduced. The phase change process in the solution is tracked by using variable temperature UV/vis. The turbidity phase transition curve is shown in fig. 3.
Embodiment III:
EtG1-POG-TPE is dissolved in water/tetrahydrofuran mixed solvent with different proportions, the concentration is 0.01mg/mL, lambda ex =350 nm. The emission spectrum of the series of solutions is obtained by testing in a constant temperature mode of a fluorescence photometer, the fluorescence intensity is obviously enhanced along with the increase of the water proportion, and the fluorescence enhancement curve is shown in figure 4.
Embodiment four:
dissolving EtG1-POG-TPE in tetrahydrofuran to obtain a solution with concentration of 0.01mg/mL and lambda ex =350 nm. The temperature change emission spectrum of the solution is obtained by testing in a temperature change mode of a fluorescence photometer, the temperature is set to be increased from 21 ℃ to 35 ℃, the fluorescence intensity is obviously enhanced, and the fluorescence enhancement curve is shown in figure 5.
Fifth embodiment:
EtG1-POG-TPE is dissolved in tetrahydrofuran to be dissolved in water, the concentration is 0.02mg/mL, 10uL is dripped on a mica sheet, nitrogen is dried for 3 hours, an Atomic Force Microscope (AFM) test is adopted, and the morphology is shown in figure 6.
The embodiments of the present invention have been described above with reference to the accompanying drawings, but the present invention is not limited to the above embodiments, and various changes, modifications, substitutions, combinations, and simplifications made according to the spirit and principles of the technical scheme of the present invention should be equivalent substitution, so long as the purposes of the present invention are met, and the technical principles of the preparation method and application of the amphiphilic polypeptide molecule of the temperature sensitive aggregation-induced emission characteristic of the present invention are not deviated, which all fall within the scope of the present invention.
Claims (3)
1. The amphiphilic polypeptide molecule with the temperature-sensitive aggregation-induced emission characteristic is characterized by having a structural formula as follows:
where x=ome or OEt, n=1.
2. The amphiphilic polypeptide molecule with temperature-sensitive aggregation-induced emission characteristics according to claim 1, wherein the microsphere size of the amphiphilic polypeptide molecule is 100-500nm.
3. A method for preparing the amphiphilic polypeptide molecule with temperature-sensitive aggregation-induced emission characteristics according to claim 1 or 2, which is characterized by comprising the following specific steps:
a. compound 1 and compound 2 were combined in the order of 1: dissolving 1 mol ratio in a proper amount of dry Dichloromethane (DCM), adding 4-5 equivalents of N, N Diisopropylethylamine (DIPEA) under the conditions of nitrogen atmosphere and ice bath, stirring at the speed of 300-500 r/min, stirring for 30min, removing the ice bath, reacting for 6-12 h, washing the reaction solution with saturated NaCl solution for 1-2 times, extracting the separated liquid with DCM, drying the organic phase with anhydrous MgSO4, filtering, purifying with silica gel column chromatography, wherein the volume ratio of DCM to MeOH in the eluent is 20:1, and evaporating the solvent to obtain a compound 3; the structural formula of the compound 1 is as follows:
the structural formula of the compound 2 is as follows:
n=1 in compound 2;
b. 1-fold equivalent of Compound 3 was dissolved in the appropriate amount of MeOH/H 2 Adding 15 times equivalent of LiOH H into the mixed solvent of O under the ice bath condition 2 O, stirring at 300-500 r/min for 30min, removing ice bath, reacting for 3-5 h, evaporating to dry reaction liquid, dissolving with pure water, and then dissolving with 10% NaSO 4 The pH of the solution was adjusted to 5 to 6, and the separated solution was extracted with DCM and then dried over anhydrous MgSO 4 Drying the organic phase, filtering, and evaporating the solvent to obtain a compound 4;
c. dissolving one equivalent of compound 4 in a proper amount of dried DCM, respectively adding 1.1 equivalent of pentafluorophenol (PfpOH) and 1.1 equivalent of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC. HCl) under the conditions of nitrogen atmosphere and ice bath, stirring at a speed of 300-500 r/min for 30min, removing the ice bath, reacting for 4-6 h, and then using saturated NaHCO 3 The reaction mixture was washed once with an aqueous solution and a saturated NaCl solution, and after separating the mixture by DCM extraction, the mixture was washed with anhydrous MgSO 4 Drying the organic phase, filtering, purifying by silica gel column chromatography, wherein the volume ratio of DCM to MeOH in the eluent is 30:1, and evaporating the solvent to obtain a compound 5;
d. dissolving a compound 5 and 1- (4-aminobenzene) -1, 2-tristyrene in N, N-Dimethylamide (DMF) according to the molar ratio of 1:1.1, adding 4-10 times equivalent of DIPEA under the nitrogen atmosphere and ice bath condition, stirring at the speed of 300-500 r/min, stirring for 30min, removing the ice bath, reacting for 6-12 h, washing the reaction solution for 1-2 times by using a saturated NaCl solution, extracting the separated solution by using the DCM, and then separating the solution by using anhydrous MgSO 4 Drying the organic phase, filtering, purifying by silica gel column chromatography, wherein the volume ratio of DCM to MeOH in the eluent is 20:1, and evaporating the solvent to obtain a final product compound 6; the structural formula of the compound 6 is as follows:
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| CN106397577A (en) * | 2016-05-16 | 2017-02-15 | 上海大学 | Dual stimuli-responsive collagen polypeptide polymer and preparation method thereof |
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