CN103897196B - Polymer and preparation method thereof - Google Patents
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- CN103897196B CN103897196B CN201210578582.2A CN201210578582A CN103897196B CN 103897196 B CN103897196 B CN 103897196B CN 201210578582 A CN201210578582 A CN 201210578582A CN 103897196 B CN103897196 B CN 103897196B
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Abstract
The present invention is applicable to polymeric material field, it is provided that a kind of polymer and preparation method thereof.Inventive polymers preparation method, including preparing the first intermediate product, preparing the second intermediate product, prepare the polymer of band carboxyl and prepare the steps such as polymer.Inventive polymers has poly-(2 methyl 2 oxazoline) and other groups, there is the highest biologically inert, can either some protein specific binding, can stop that remaining macromolecular substances non-specific binding is on its surface, it is possible to for accurate, sensitive, quantitative and efficient immunology detection simultaneously；Polymerization process for preparing of the present invention, obtain that there is poly-(2 methyl 2 oxazoline) and the polymer of other groups by polyreaction, realize this polymer and there is the highest biologically inert, can either some protein specific binding, can stop that remaining macromolecular substances non-specific binding is on its surface, it is possible to for accurate, sensitive, quantitative and efficient immunology detection simultaneously.
Description
Technical field
The invention belongs to field of new, particularly relate to a kind of polymer and preparation method thereof.
Background technology
In recent years, the detection of blood circulation tumor cell becomes the focus that biomedical sector is paid close attention to.It is known that
Following process is typically experienced in the generation evolution of cancer.First it is primary carcinoid generation, next to that tumor
The angiogenesis of tissue, the followed by formation of primary malignant neoplasm, is that malignant cell invades blood vessel by basement membrane again
Becoming blood circulation tumor cell, last malignant cell invades remaining normal structure by blood vessel wall and forms Secondary cases evil
Property tumor.Second malignant neoplasm is once formed, and excision just loses meaning, and the treatment of cancer becomes extremely difficult.Logical
In the case of Chang, the circulating tumor cell in blood can stop the longer time in blood, just can invade remaining normal structure
Form second malignant neoplasm.Therefore, the detection of blood circulation tumor cell is increasingly becoming cancer diagnosis and determines therapeutic scheme
An important indicator.Additionally, by the monitoring of blood circulation tumor cell concentration in cancer patient, it is also possible to anticarcinogen
The curative effect of thing is estimated.Due to the least (every 10 ten thousand to 10 hundred million blood cells of circulating tumor cell concentration in blood
Plant and have one), therefore the screening of circulating tumor cell becomes a challenging problem.Current major programme is to utilize
Circulating tumor cell is thin with the difference of the volume size of normal blood cell and circulating tumor cell epithelium the most anti-with some antibody
The specific binding effect of intercellular adhesion molecule, antikeratin antibody etc. is sieved.For first scheme, need to solve
Problem be prepare can some biomacromolecule specific binding, simultaneously can stop remaining biomacromolecule non-specific binding
Material.In recent years, immunology detection chip becomes the focus that biomedical sector is paid close attention to.Accurately, sensitive, quantitative, high
The immunology detection of effect is always the target that people are pursued.Equally, in order to reach above requirement, immunology chip needs tool
Standby can some protein molecular specific binding, the surface of remaining biomacromolecule non-specific binding can be stopped simultaneously.
At present, the material of this respect is actually rare.
Summary of the invention
In view of this, it is an object of the invention to provide one can some biomacromolecule specific binding, with
Time can stop the macromolecular material of remaining biomacromolecule non-specific binding.
The present invention is achieved in that
A kind of polymer, has a following structural formula:
This x, y, z is selected from the natural number of 1-500, and x+y+z is the natural number of 50-500.
And, above-mentioned method for producing polymer, comprise the steps:
2-methyl-2-oxazoline and initiator are added to organic solvent, under the conditions of temperature is 60-80 DEG C, reacts 6-
48 hours, temperature is adjusted to room temperature, add terminator, stirring reaction 2-24 hour, solvent in solution after reaction is removed, added
Water stirs, and the product after the stirring that adds water is hydrolyzed 2-36 hour under the conditions of pH value is 9-14, solution ph after hydrolyzing
Adjusting to 6-8, dialysis is dried to obtain the first intermediate product, and this initiator is selected from 3-ethyl bromide or 3-methyl bromide c, should
Terminator is selected from two ends all with the polymer such as ethylenediamine of amino, butanediamine, hexamethylene diamine；
Obtain the first solution by soluble in water for this first intermediate product, folic acid or biotin are dissolved in dimethyl sulfoxide or two
In methylformamide and add N-(3-dimethylamino-propyl)-N '-ethyl-carboddiimide hydrochlorate stirring obtains the second solution,
This second solution is added to the first solution, at room temperature reaction 2-48 hour, solution dialysis after reaction is obtained in second
Between product；
2-methyl-2-oxazoline and initiator are added to organic solvent, under the conditions of temperature is 60-80 DEG C, reacts 6-
48 hours, temperature is adjusted to room temperature, add terminator, stirring reaction 2-24 hour, solvent after reaction is removed, adds water and stir
Mixing, the product after the stirring that adds water hydrolyzed 2-36 hour under the conditions of pH value is 9-14, after hydrolyzing, solution ph adjusts
To 6-8, dialysis is dried to obtain the polymer of band ester group, and this initiator is selected from Methyl triflate or iodomethane, this terminator
It is selected from 4-piperidine carboxylate, 4-piperazine with primary amine or secondary amine, another end with the polymer of ester group selected from an end
Pyridine carboxylate methyl ester, glycine ethyl ester, glycine methyl ester, 3-alanine ethyl ester, 3-aminopropanoate etc.；
The bromate of PLL is added to buffer, adds polymer and this second centre of this band carboxyl
Product, adds N-(3-dimethylamino-propyl)-N '-ethyl-carboddiimide hydrochlorate and N-hydroxy-succinamide sulfonate sodium,
Reaction 1-32 hour at ambient temperature, after reacting, solution dialysis is dried, and obtains polymer.
Inventive polymers, has poly-(2-methyl-2-oxazoline) and other groups, has the highest biologically inert, both
Can some protein specific binding, simultaneously can stop that remaining macromolecular substances non-specific binding is at its surface, energy
It is enough in accurate, sensitive, quantitative and efficient immunology detection；Polymerization process for preparing of the present invention, is had by polyreaction
There are poly-(2-methyl-2-oxazoline) and the polymer of other groups, it is achieved this polymer has the highest biologically inert, can either
Some protein specific binding, can stop that remaining macromolecular substances non-specific binding is on its surface simultaneously, it is possible to use
In accurate, sensitive, quantitative and efficient immunology detection.
Accompanying drawing explanation
Fig. 1 is the polymer of the embodiment of the present invention one preparation1H-nuclear magnetic spectrum.
Detailed description of the invention
In order to make the purpose of the present invention, technical scheme and advantage clearer, below in conjunction with drawings and Examples, right
The present invention is further elaborated.Should be appreciated that specific embodiment described herein only in order to explain the present invention, and
It is not used in the restriction present invention.
The embodiment of the present invention provides a kind of polymer, and this polymer has following structural formula:
This x, y, z is selected from the natural number of 1-500, and x+y+z is the natural number of 50-500.This polymer can be regarded as
The copolymer of three kinds of repetitives representated by x, y, z, for random copolymer, rather than block copolymer.
Inventive polymers, has poly-(2-methyl-2-oxazoline) and other groups, has the highest biologically inert, both
Can some protein specific binding, simultaneously can stop that remaining macromolecular substances non-specific binding is at its surface, energy
It is enough in accurate, sensitive, quantitative and efficient immunology detection.
The embodiment of the present invention further provides for above-mentioned method for producing polymer, comprises the steps:
Step S01, prepares the first intermediate product:
2-methyl-2-oxazoline and initiator are added to organic solvent, under the conditions of temperature is 60-80 DEG C, reacts 6-
48 hours, temperature is adjusted to room temperature, add terminator, stirring reaction 2-24 hour, the solvent in solution after reaction is removed,
Add water stirring, the product after the stirring that adds water is hydrolyzed 2-36 hour under the conditions of pH value is 9-14, pH value of solution after hydrolyzing
Value adjusts to 6-8, and dialysis is dried to obtain the first intermediate product, and this initiator is selected from 3-ethyl bromide or 3-methyl bromide c,
This terminator selected from two ends all with the polymer of amino, these two ends all with the polymer such as ethylenediamine of amino,
Butanediamine or hexamethylene diamine etc.；
Step S02, prepares the second intermediate product:
Obtain the first solution by soluble in water for this first intermediate product, folic acid or biotin are dissolved in dimethyl sulfoxide or two
In methylformamide and add N-(3-dimethylamino-propyl)-N '-ethyl-carboddiimide hydrochlorate stirring obtains the second solution,
This second solution is added to the first solution, at room temperature reaction 2-48 hour, solution dialysis after reaction is obtained in second
Between product；
Step S03, prepares the polymer of band carboxyl:
2-methyl-2-oxazoline and initiator are added to organic solvent, under the conditions of temperature is 60-80 DEG C, reacts 6-
48 hours, temperature is adjusted to room temperature, add terminator, stirring reaction 2-24 hour, solvent after reaction is removed, adds water and stir
Mixing, the product after the stirring that adds water hydrolyzed 2-36 hour under the conditions of pH value is 9-14, after hydrolyzing, solution ph adjusts
To 6-8, dialysis is dried to obtain the polymer of band carboxyl, and this initiator is selected from Methyl triflate or iodomethane, this terminator
Selected from an end with primary amine or secondary amine, another end, with the polymer of ester group, is selected from 4-piperidine carboxylate,
4-piperidine carboxylic acid methyl ester, glycine ethyl ester, glycine methyl ester, 3-alanine ethyl ester, 3-aminopropanoate etc..
S04, prepares polymer:
The bromate of PLL is added to buffer, adds polymer and this second centre of this band carboxyl
Product, adds N-(3-dimethylamino-propyl)-N '-ethyl-carboddiimide hydrochlorate and N-hydroxy-succinamide sulfonate sodium,
Reaction 1-32 hour at ambient temperature, after reacting, solution dialysis is dried, and obtains polymer.
In step S01, the mol ratio of this initiator and 2-methyl-2-oxazoline is 0.8-4:100, this terminator and 2-first
The mol ratio of base-2-oxazoline is 4-100:100.This organic solvent is selected from acetonitrile or dimethylformamide.
Step S01 is specific as follows:
After 2-methyl-2-oxazoline and initiator for reaction are completed, system temperature is adjusted to room temperature, such as 20-30 DEG C,
Terminator, then stirring 2-24 hour is added in reaction system.After reacting, solvent evaporates, after making reaction under condition of negative pressure
Organic solvent in solution removes, and obtains oily thick liquid, adds water, stirring, mixed in this oily thick liquid
Solution, hydrolyzes this mixed solution 2-36 hour under the conditions of pH value is 9-14, solution ph after hydrolysis is adjusted to 6-8, will
The solution adjusting pH to 6-8 is inserted in bag filter, dialysis treatment in deionized water, more than 3 days time, obtains producing in the middle of first
Thing.
In step S02, the mol ratio of this first intermediate product and described folic acid or biotin is 1:2-5.Step S02 is concrete
As follows:
By soluble in water for this first intermediate product, stirring obtains the first solution；
Then folic acid or biotin it is dissolved in dimethyl sulfoxide or dimethylformamide and adds N-(3-dimethylamino third
Base)-N '-ethyl-carboddiimide hydrochlorate stirring obtains the second solution；
This second solution is added to the first solution, is stirred at room temperature, reacts 2-48 hour, solution after reaction is turned
Enter in bag filter, in deionized water dialysis more than 3 days, by the solution lyophilization containing polymer, obtain producing in the middle of second
Thing；
In step S03, the mol ratio of this initiator and described 2-methyl-2-oxazoline is 0.8-4:100；This terminator and
The mol ratio of 2-methyl-2-oxazoline is 4-100:100.This organic solvent is identical with in step S01, does not repeat at this to illustrate.
Step S03 is specific as follows:
After 2-methyl-2-oxazoline and initiator for reaction are completed, system temperature is adjusted to room temperature, such as 20-30 DEG C,
Terminator, then stirring 2-24 hour is added in reaction system.After reacting, solvent evaporates, after making reaction under condition of negative pressure
Organic solvent in solution removes, and obtains oily thick liquid, adds water, stirring, mixed in this oily thick liquid
Solution, hydrolyzes this mixed solution 2-36 hour under the conditions of pH value is 9-14, solution ph after hydrolysis is adjusted to 6-8, will
The solution that pH adjusts to 6-8 is inserted in bag filter, and dialysis treatment in deionized water obtains carboxylic polymer；
In step S04, the mol ratio of the bromate of this PLL and the polymer of described band carboxyl is 1:
0.002-0.5；The bromate of this PLL and the mol ratio of described second intermediate product are 1:0.002-0.5;This gathers
The bromate of (1B) and N-(3-dimethylamino-propyl) mol ratio of-N '-ethyl-carboddiimide hydrochlorate is 1:
0.02-10, the bromate of this PLL and be 1:0.004-with the mol ratio of N-hydroxy-succinamide sulfonate sodium
0.5.This buffer is preferably the phosphate buffer of 0.01mol/L, pH=7.4.
In step S04, after having reacted, solution after reaction is transferred in bag filter, respectively at phosphate buffer and
In deionized water dialyse more than 3 days, the liquid freezing containing polymer is dried, obtains polymer, this phosphate buffer and
Same as before, do not repeat at this to illustrate.
Polymerization process for preparing of the present invention, obtains having poly-(2-methyl-2-oxazoline) and other groups by polyreaction
Polymer, it is achieved this polymer has the highest biologically inert, can either some protein specific binding, can hinder simultaneously
Keep off remaining macromolecular substances non-specific binding on its surface, it is possible to examine for accurate, sensitive, quantitative and efficient immunology
Survey.
Below in conjunction with specific embodiment, above-mentioned method for producing polymer is described in detail.
Embodiment one
The chemical structural formula of embodiment of the present invention polymer is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
1, the synthesis of poly-(the 2-methyl-2-oxazoline) of two end band carboxyls respectively and amino:
2-methyl-2-oxazoline (8.5mL, 100mmol) is dissolved in acetonitrile (30mL), then by 3-ethyl bromide
(0.520mL, 4mmol) joins in reaction system, heats the mixture to 70 DEG C afterwards, reacts 8 hours.Stop subsequently adding
Heat, thing to be mixed is cooled to room temperature, adds ethylenediamine (6.65mL, 100mmol) and stirs 12 hours.Under negative pressure with heating by portion
Divide solvent to remove, obtain oily thick liquid.Add deionized water to after 50mL, hydrolyze 24 hours under conditions of pH=14,
PH value of solution is adjusted to neutrality, then the solution containing polymer is transferred in bag filter, in deionized water dialysis 24 hours.?
After, the solution lyophilization containing polymer or heating under reduced pressure are dried, obtain the poly-(2-methyl-2-that molecular weight is about 2K
Oxazoline) white solid, structural formula is as follows:
2, the synthesis of modified with folic acid poly-(2-methyl-2-oxazoline):
By poly-(2-methyl-2-oxazoline) white solid of two ends band carboxyl respectively obtained above and amino (2K,
0.20g, 0.1mmol) it is dissolved in deionized water (6.0mL) to prepare the aqueous solution of polymer.Again by folic acid (132mg,
0.3mmol) it is dissolved in dimethyl sulfoxide (4.0mL), adds N-(3-dimethylamino-propyl afterwards)-N '-ethyl-carboddiimide
Hydrochlorate (577mg, 3.0mmol), stirring is to being completely dissolved.Then the solution containing folic acid is all added in polymer solution,
At room temperature reaction 48 hours.After reaction terminates, the solution containing polymer is transferred in bag filter, the most thoroughly
Analyse 7 days.Finally, by the solution lyophilization containing polymer, obtain molecular weight be about the modified with folic acid of 2.5K poly-(2-methyl-
2-oxazoline) yellow solid, structural formula is as follows:
3,2-methyl-2-oxazoline (8.5mL, 100mmol) is dissolved in acetonitrile (30mL), then by Methyl triflate
(0.44mL, 4mmol) joins in reaction system, heats the mixture to 70 DEG C afterwards, reacts 8 hours.Stop heating subsequently,
Thing to be mixed is cooled to room temperature, adds 4-piperidine carboxylate (1.224mL, 8mmol) and stirs 12 hours.Under negative pressure with heating
Partial solvent is removed, obtains oily thick liquid.Add deionized water to after 50mL, under conditions of pH=14, hydrolyze 24
Hour, pH value of solution being adjusted to neutrality, then the solution containing polymer is transferred in bag filter, dialysis 24 is little in deionized water
Time.Finally, the solution lyophilization containing polymer or heating under reduced pressure are dried, obtain the poly-(2-methyl-2-that molecular weight is 2K
Oxazoline) white solid, structural formula is as follows:
4, PLL-grafting-poly-(2-methyl-2-oxazoline) modified with folic acid poly-(2-methyl-2-oxazoline)
Synthesis:
The bromate (molecular weight 21K, 21mg, 1 μm ol) of PLL is dissolved in 3mL phosphate-buffered salt
In (0.01mol/L, pH=7.4) solution, addition molecular weight is 2K, the simple function reunion (2-of the end strips carboxyl of step 3 preparation
Methyl-2-oxazoline) (48mg, 24 μm ol) and modified with folic acid obtained above poly-(2-methyl-2-oxazoline) (2.5K, 15mg,
6 μm ol).Add N-(3-dimethylamino-propyl)-N '-ethyl-carboddiimide hydrochlorate (57.6mg, 300 μm ol) and N-hydroxyl
Base butanimide sulfonate sodium (6.51mg, 30 μm ol), at room temperature reaction 16 hours.After reaction terminates, will be containing polymerization
The solution of thing is transferred in bag filter, dialysis 7 in phosphate-buffered salt (0.01mol/L, pH=7.4) solution and deionization respectively
My god.Finally, by the solution lyophilization containing polymer, obtaining molecular weight is 80K PLL-grafting-poly-(2-first
Base-2-oxazoline) and modified with folic acid poly-(2-methyl-2-oxazoline) yellow solid (grafting density 0.3, wherein modified with folic acid gather
(2-methyl-2-oxazoline) accounts for 20%).
Refer to Fig. 1, Fig. 1 and show the polymer nuclear magnetic spectrogram prepared by the embodiment of the present invention, it will be seen from figure 1 that on
Stating the polymer prepared by preparation method is the polymer that structure above is characterized.
The polymer obtained prepared by the embodiment of the present invention one, can be used for circulating tumor cell in preparation detection blood
Biochip.Transition metal oxide such as tantalum pentoxide, niobium pentaoxide, titanium dioxide, indium tin oxide target and silicon dioxide etc.
Surface is with negative charge in physiological conditions, and PLL is with positive charge.PLL-grafting-folic acid is repaiied
Adorn the weak solution of poly-(2-methyl-2-oxazoline) and drop in the silica chip or plating processed through Piranha solution oxide
There are the silica chip surface of any of the above transition metal oxide, poly-(the 2-first of PLL-grafting-modified with folic acid
Base-2-oxazoline) under electrostatic interaction, meeting Spontaneous adsorption, to electronegative surface, forms monolayer.Due to poly-(2-methyl-
2-oxazoline) non-specific adsorption of biomolecule can be stopped, simultaneously fixing folate molecule can be with mistake on tumor cell membrane
The folacin receptor that degree is expressed is specific binding, this material the circulating tumor that the chip prepared can optionally adsorb in blood
Cell.Additionally, combine the technology such as immunofluorescence dyeing method, polymerase chain reaction, optical waveguide optical spectroscopy, can be to screening out
Circulating tumor cancerous cell carry out molecular biology or physicochemical properties are analyzed.
Embodiment two
The chemical structural formula of embodiment of the present invention polymer is as follows:
Embodiment of the present invention method for producing polymer, comprises the steps:
1, the synthesis of poly-(the 2-methyl-2-oxazoline) of two end band carboxyls respectively and amino:
2-methyl-2-oxazoline (8.5mL, 100mmol) is dissolved in acetonitrile (30mL), then by 3-ethyl bromide
(0.520mL, 4mmol) joins in reaction system, heats the mixture to 70 DEG C afterwards, reacts 8 hours.Stop subsequently adding
Heat, thing to be mixed is cooled to room temperature, adds ethylenediamine (6.65mL, 100mmol) and stirs 12 hours.Under negative pressure with heating by portion
Divide solvent to remove, obtain oily thick liquid.Add deionized water to after 50mL, hydrolyze 24 hours under conditions of pH=14,
PH value of solution is adjusted to neutrality, then the solution containing polymer is transferred in bag filter, in deionized water dialysis 24 hours.?
After, the solution lyophilization containing polymer or heating under reduced pressure are dried, obtain the poly-(2-methyl-2-that molecular weight is about 2K
Oxazoline) white solid, structural formula is as follows:
2, the synthesis of biotin modification poly-(2-methyl-2-oxazoline):
By poly-(2-methyl-2-oxazoline) white solid of two ends band carboxyl respectively obtained above and amino (2K,
0.20g, 0.1mmol) it is dissolved in deionized water (6.0mL) to prepare the aqueous solution of polymer.Again by biotin (73mg,
0.3mmol) it is dissolved in dimethyl sulfoxide (4.0mL), adds N-(3-dimethylamino-propyl afterwards)-N '-ethyl-carboddiimide
Hydrochlorate (577mg, 3.0mmol), stirring is to being completely dissolved.Then the solution containing biotin is all added polymer solution
In, at room temperature reaction 48 hours.After reaction terminates, the solution containing polymer is transferred in bag filter, at deionized water
Middle dialysis 7 days.Finally, by the solution lyophilization containing polymer, the poly-(2-of biotin modification that molecular weight is about 2.2K is obtained
Methyl-2-oxazoline) white solid, structural formula is as follows:
3,2-methyl-2-oxazoline (8.5mL, 100mmol) is dissolved in acetonitrile (30mL), then by Methyl triflate
(0.44mL, 4mmol) joins in reaction system, heats the mixture to 70 DEG C afterwards, reacts 8 hours.Stop heating subsequently,
Thing to be mixed is cooled to room temperature, adds 4-piperidine carboxylate (1.224mL, 8mmol) and stirs 12 hours.Under negative pressure with heating
Partial solvent is removed, obtains oily thick liquid.Add deionized water to after 50mL, under conditions of pH=14, hydrolyze 24
Hour, pH value of solution being adjusted to neutrality, then the solution containing polymer is transferred in bag filter, dialysis 24 is little in deionized water
Time.Finally, the solution lyophilization containing polymer or heating under reduced pressure are dried, obtain the poly-(2-methyl-2-that molecular weight is 2K
Oxazoline) white solid, structural formula is as follows:
4, PLL-grafting-poly-(2-methyl-2-oxazoline) the poly-(2-methyl-2-azoles of biotin modification
Quinoline) synthesis:
The bromate (molecular weight 21K, 21mg, 1 μm ol) of PLL is dissolved in 3mL phosphate-buffered salt
(in 0.01mol/L, pH=7.4 solution, addition molecular weight is 2K, simple function reunion (the 2-first of the end strips carboxyl of step 3 preparation
Base-2-oxazoline) (48mg, 24 μm ol) and biotin modification obtained above poly-(2-methyl-2-oxazoline) (2.2K,
13.2mg, 6 μm ol).Add N-(3-dimethylamino-propyl)-N '-ethyl-carboddiimide hydrochlorate (57.6mg, 300 μm ol)
With N-hydroxy-succinamide sulfonate sodium (6.51mg, 30 μm ol), at room temperature reaction 16 hours.After reaction terminates, will contain
The solution having polymer is transferred in bag filter, respectively at phosphate-buffered salt (0.01mol/L, pH=7.4) solution and deionized water
Middle dialysis 7 days.Finally, by the solution lyophilization containing polymer, obtaining molecular weight is 80K PLL-grafting-poly-
(2-methyl-2-oxazoline) biotin modification poly-(2-methyl-2-oxazoline) white solid (grafting density 0.3, wherein biological
Element is modified poly-(2-methyl-2-oxazoline) and is accounted for 20%).
The nuclear magnetic spectrogram of the polymer prepared by the embodiment of the present invention two is similar with aforesaid, does not repeat at this to illustrate.Should
This material of polymer can be used for antigen or the biochip of antibody protein in preparation detection blood.Transition metal oxide such as five oxygen
Change the surface in physiological conditions such as two tantalums, niobium pentaoxide, titanium dioxide, indium tin oxide target and silicon dioxide with negative charge, poly-
(1B) is with positive charge.Dilute molten by poly-for PLL-grafting-biotin modification (2-methyl-2-oxazoline)
Drop is in the silica chip processed through Piranha solution oxide or is coated with any of the above transition metal oxide
Silica chip surface, PLL-grafting-biotin modification poly-(2-methyl-2-oxazoline) is under electrostatic interaction
Meeting Spontaneous adsorption, to electronegative surface, forms monolayer.Owing to fixing biotin molecule can select with streptavidin
Selecting property combines, and the most poly-(2-methyl-2-oxazoline) can stop the non-specific adsorption of biomolecule, and streptavidin is modified
Antibody or antigen protein can be fixed to, by the affinity interaction with fixing biotin, the chip list prepared by this material
Face such that it is able to optionally corresponding antigen or antibody protein in absorption blood.In conjunction with immunofluorescence dyeing method, light wave
The technology such as guide-lighting spectroscopy, antigens various in blood or antibody protein can be carried out accurate, sensitive, quantitative, analyze efficiently.
The foregoing is only presently preferred embodiments of the present invention, not in order to limit the present invention, all essences in the present invention
Any amendment, equivalent and the improvement etc. made within god and principle, should be included within the scope of the present invention.
Claims (9)
1. a polymer, has a following structural formula:
Described x, y, z is selected from the natural number of 1-500, and x+y+z is the natural number of 50-500.
2. method for producing polymer as claimed in claim 1, comprises the steps:
2-methyl-2-oxazoline and initiator are added to organic solvent, under the conditions of temperature is 60-80 DEG C, reacts 6-48 little
Time, temperature is adjusted to room temperature, add terminator, stirring reaction 2-24 hour, solvent in solution after reaction is removed, added water and stir
Mixing, the product after the stirring that adds water hydrolyzed 2-36 hour under the conditions of pH value is 9-14, after hydrolyzing, solution ph adjusts
To 6-8, dialysis is dried to obtain the first intermediate product, and described initiator is selected from 3-ethyl bromide or 3-methyl bromide c, described
Terminator is selected from two ends all with the polymer of amino；
Obtain the first solution by soluble in water for described first intermediate product, folic acid or biotin are dissolved in dimethyl sulfoxide or diformazan
In base Methanamide and add N-(3-dimethylamino-propyl)-N '-ethyl-carboddiimide hydrochlorate, stirring obtains the second solution, will
Described second solution adds in the first solution, at room temperature reaction 2-48 hour, is dialysed by solution after reaction and is dried to obtain the
Two intermediate products；
2-methyl-2-oxazoline and initiator are added to organic solvent, under the conditions of temperature is 60-80 DEG C, reacts 6-48 little
Time, temperature is adjusted to room temperature, add terminator, stirring reaction 2-24 hour, solvent after reaction is removed, add water stirring, general
The product after stirring that adds water hydrolyzes 2-36 hour under the conditions of pH value is 9-14, adjusts solution ph after hydrolysis to 6-8,
Dialysis is dried to obtain the polymer of band carboxyl, and described initiator is selected from Methyl triflate or iodomethane, and described terminator selects
From an end with primary amine group or secondary amine group, another end is with the polymer of ester group；
The bromate of PLL is added to buffer, adds in the middle of the polymer and described second of described band carboxyl
Product, adds N-(3-dimethylamino-propyl)-N '-ethyl-carboddiimide hydrochlorate and N-hydroxy-succinamide sulfonate sodium,
Reaction 1-32 hour at ambient temperature, after reacting, solution dialysis is dried, and obtains polymer.
3. method for producing polymer as claimed in claim 2, it is characterised in that prepare in described first intermediate product step, institute
The mol ratio stating initiator and described 2-methyl-2-oxazoline is 0.8-4:100.
4. method for producing polymer as claimed in claim 2, it is characterised in that prepare in described first intermediate product step, institute
The mol ratio stating terminator and described 2-methyl-2-oxazoline is 4-100:100.
5. method for producing polymer as claimed in claim 2, it is characterised in that described first intermediate product and described folic acid or life
The mol ratio of thing element is 1:2-5.
6. as claimed in claim 2 method for producing polymer, it is characterised in that the bromate of described PLL and described
The mol ratio of the polymer with carboxyl is 1:0.002-0.5.
7. as claimed in claim 2 method for producing polymer, it is characterised in that the bromate of described PLL and described
The mol ratio of the second intermediate product is 1:0.002-0.5.
8. method for producing polymer as claimed in claim 2, it is characterised in that prepare in the polymer step of described band carboxyl,
One end is selected from 4-piperidine carboxylic acid second with primary amine group or secondary amine group, another end with the polymer of ester group
Ester, 4-piperidine carboxylic acid methyl ester, glycine ethyl ester, glycine methyl ester, 3-alanine ethyl ester or 3-aminopropanoate.
9. method for producing polymer as claimed in claim 2, it is characterised in that prepare in the polymer step of described band carboxyl,
The mol ratio of described initiator and described 2-methyl-2-oxazoline is 0.8-4:100；Described terminator and described 2-methyl-2-
The mol ratio of oxazoline is 4-100:100.
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| CN201210578582.2A CN103897196B (en) | 2012-12-27 | 2012-12-27 | Polymer and preparation method thereof |
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| Formation and characterization of DNA-polymer-condensates based on poly(2-methyl-2-oxazoline) grafted poly(L-lysine) for non-viral delivery of therapeutic DNA;Thomas von Erlach et al.;《Biomaterials》;20110422;第32卷;5292 * |
| Poly-2-methyl-2-oxazoline: a peptide-like polymer for protein-repellent sulfaces;Rupert Konradi et al.;《Langmuir》;20080801;第24卷(第03期);614 * |
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