CN101575412A - Hyperbranched polyamino acid, preparation method and application thereof - Google Patents
Hyperbranched polyamino acid, preparation method and application thereof Download PDFInfo
- Publication number
- CN101575412A CN101575412A CNA2009100627021A CN200910062702A CN101575412A CN 101575412 A CN101575412 A CN 101575412A CN A2009100627021 A CNA2009100627021 A CN A2009100627021A CN 200910062702 A CN200910062702 A CN 200910062702A CN 101575412 A CN101575412 A CN 101575412A
- Authority
- CN
- China
- Prior art keywords
- polyamino acid
- hyperbranched polyamino
- amino acid
- lys
- arg
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Peptides Or Proteins (AREA)
- Polyamides (AREA)
Abstract
The invention relates to hyperbranched polyamino acid. The chemical composition is as follows: in the formula of (Lys-)a-(-Arg-)b-(-His-)c-(-X)d, Lys, Arg and His are respectively lysine, arginine and histidine, X is one of or a plurality of any amino acids except for the amino acids above, wherein a is not less than 0.2 and not more than 0.95, b is not less than 0 and not more than 0.8, c is not less than 0 and not more than 0.8, d is not less than 0 and not more than 0.3, and the sum of a, b, c and d is 1. The preparation method is as follows: uniformly mixing lysine or lysine salt with other amino acids or the amino acid salts contained in the hyperbranched polyamino acid to react for 2-64h at the temperature of 130-180 DEG C and then obtain yellow solid, and finally purifying the coarse product with a precipitation method to obtain the hyperbranched polyamino acid. The hyperbranched polyamino acid obtained in the invention can be used as nonviral gene carrier for the transduction of huamn or animal cell gene, and the hyperbranched polyamino acid nonviral gene carrier provided by the invention is reasonable in design, simple in preparation method, high in transfection efficiency, low cytotoxicity and favorable transduction efficiency in the presence of blood serum.
Description
Technical field
The present invention relates to non-viral gene vector, specifically relating to chemical constitution is non-viral gene vector of hyperbranched polyamino acid and its production and application.
Background technology
Gene therapy is by suitable carriers goal gene to be delivered in patient's body to carry out suitable expression in particular organization's cell (target cell), to correct or to improve the defective that this Disease-causing gene is produced, reaches the purpose of treatment disease.Gene therapy has obtained remarkable progress on semicentennial road for development, also run into a lot of difficulties.At present, gene therapy will enter the practical stage, also has some root problems to need to solve.Wherein, safely, the structure of genophore is one of sixty-four dollar question efficiently.In general, gene delivery system is divided into two classes, virus carrier system and non-virus carrier system.Non-virus carrier mainly relies on the liposome of the polymkeric substance of positively charged or positively charged to combine the mixture that forms a certain size with DNA and carries.But because the structure of liposome DNA mixture is very complicated, transfection efficiency instability in the complex environment in vivo, thereby successful in actual applications example and few.Find in the research that some cationic polymerss can form nano level mixture and help the DNA transfection with DNA, as polylysine (PLL), polymine (PEI), pamam dendrimer molecule, protamine etc.These cationic polymerss are widespread use in outer-gene transmits all.Wherein, tree-like polymer has the characteristics of compound with regular structure, the molecule periphery distributing much can be protonated amino, make it carry out effective the combination with DNA.But preparation process complexity and preparation cost height are restricted tree-like high molecular application.Hyperbranched polymers then can obtain a large amount of products by low-molecular-weight raw material by single step reaction, and its synthesis step is much simple with respect to tree-like polymer.
People are finding coming from transcribing in the proteic research of trans-activating factor (Tat) of HIV-1 virus, why Tat albumen can spontaneously pass through cytolemma is because it contains the peptide chain by 10 to 16 particular sequences that amino acid is formed, this class peptide chain be called as cell pass through peptide (cell-penetrating peptide, CPP).CPP is mainly by arginine, and basic aminoacidss such as Methionin are formed, and wherein arginic effect is particularly important.In recent years, a lot of research institutions begin to pay close attention to the performance of passing through of CPP cell membrane, and studies show that, much contain the many polypeptide of arginine and have shown very strong cell-penetrating ability.It is generally acknowledged, between the guanidine radicals side group of arginic positively charged and the cell except electrostatic interaction owing to have a leg-of-mutton geometry, can also with the stronger hydrogen bond of phosphate-based formation on the cytolemma, thereby promote passing through of cell membrane.
The present invention is raw material with the natural amino acid, prepares the hyperbranched cationic polymers that has similar cell-penetrating peptides and high surge capability is arranged by the method for simple thermal polycondensation in endosome, to obtain the genophore of high-efficiency low-toxicity.
Summary of the invention
The object of the invention provides a kind of technology hyperbranched polyamino acid simple, with low cost and its production and application.
The object of the invention provides the hyperbranched polyamino acid as genophore.
Hyperbranched polyamino acid non-viral gene vector provided by the invention, its chemical constitution has following general formula:
Lys, Arg, His are respectively Methionin, arginine, Histidine in the formula, X is any or several seed amino acids except that above-mentioned amino acid, a, b, c, d is respectively Methionin, arginine, Histidine and other any or molar fraction (a+b+c+d=1,0.2≤a≤0.95,0≤b≤0.8,0≤c≤0.8,0≤d≤0.3) of multiple amino acids in this polymkeric substance.
The preparation method of hyperbranched polyamino acid non-viral gene vector provided by the invention, after comprising the steps: that other amino acid of containing in the chemical constitution with Methionin or lysine salt and above-mentioned hyperbranched polyamino acid or its amino acid salts mix, carry out thermal polycondensation at 130～180 ℃ of reacting by heating mixtures, after reacting 2～64 hours under this temperature, obtain hyperbranched polyamino acid; The mol ratio of other amino acid of any that contains in the chemical constitution of Methionin or lysine salt and described hyperbranched polyamino acid or its amino acid salts is 1: 0～20, and amino acid or its amino acid salts raw material consumption that b, c in the chemical constitution of 1: 0 described hyperbranched polyamino acid of expression wherein or d are 0 o'clock correspondence are 0.
Hyperbranched polyamino acid provided by the invention is characterized in that at molecular weight Mw be 1.0 * 10
3G/mol～1.0 * 10
5Has transduction efficiency preferably in the scope of g/mol.
Hyperbranched polyamino acid provided by the invention combines the application as genophore with foreign gene:
Hyperbranched polyamino acid by suitable transduction method, can be brought goal gene into human body cell and various animal and plant cells as genophore, is used for human body gene treatment and vegeto-animal gene transfer.
(1) human body of hyperbranched polyamino acid genophore and zooblast gene transfer: hyperbranched polyamino acid is combined formed mixture and human body and zooblast with foreign gene (DNA or RNA) cultivate altogether, mixture can be transduceed into cell.The result shows effectively transducible gene of hyperbranched polyamino acid, and can efficiently express in cell.
(2) vegetable cell of hyperbranched polyamino acid genophore transduction: hyperbranched polyamino acid is combined formed mixture and vegetable cell carry out co-cultivation with foreign gene, can effectively transduce vegetable cell and realize expression of gene of hyperbranched polyamino acid.
Technique effect of the present invention:
One, the present invention prepares hyperbranched polyamino acid, compares the method for other polyamino acid preparations, reacts more simple, and can obtain having the hyperbranched polyamino acid of multiple functional group.
Two, contain a large amount of Methionins in the hyperbranched polyamino acid that the present invention obtains.Have on the Methionin α-, ε-two amino can form amido linkage and obtain hyperbranched polyamino acid with carboxyl.α on the Methionin monomer-and the pKa value of epsilon-amino be respectively 9.1 and 10.5, under physiological condition, can form mixture closely by electrostatic interaction so be rich in the polyamino acid of Methionin, thereby have the effect of the efficient DNA of transduction with electronegative DNA.
Three, on the Histidine that the present invention adopts an imidazole group is arranged, the pKa value is 6.0, can serve as in the intracellular of slant acidity " proton sponge ".The present invention adopts the hyperbranched polyamino acid that is rich in Histidine of thermopolymerization method one step preparation to have stronger surge capability at pH 5～6, after carrying DNA and entering cell, can promote mixture to escape rapidly from lysosome, thereby effectively strengthen transduction efficiency.
Four, be rich in guanidine radicals in the arginine that the present invention adopts, its pKa value is 12.5, is the strongest amino acid of alkalescence.It is generally acknowledged, between the guanidine radicals side group of arginic positively charged and the cell except electrostatic interaction owing to have a leg-of-mutton geometry, can also with the stronger hydrogen bond of phosphate-based formation on the cytolemma, thereby promote passing through of cell membrane.Hyperbranched polyamino acid among the present invention is rich in the effect that arginic structure can play similar cell-penetrating peptides, significantly strengthens the expression of DNA in cell.
Five, a lot of amino residues are arranged on the synthetic hyperbranched polyamino acid of the present invention, the existence of these amino makes the compound possibility that becomes of hyperbranched polyamino acid and DNA and other genomic medicines.If other parts on the bonding then can further become multi-functional non-viral gene vector again.
Advantage of the present invention: 1. in physiological environment, amino in the hyperbranched polyamino acid that is provided and guanidine radicals are by protonated and positively charged, be a kind of cationic polymers of high charge density, can effectively be combined into nano level mixture with DNA and other genomic medicines.2. in polymkeric substance, introduce imidazolyl, can improve its surge capability in the weak acid environment of endosome, mixture can be escaped away from lysosome fast.3. be rich in guanidine radicals in the polymkeric substance, can promote passing through of carrier cell membrane.5. compare with traditional genophore, the DNA loading capacity of hyperbranched polyamino acid is big, the transduction efficiency height, and non-immunogenicity, cytotoxicity are low, and have advantages such as biodegradability.6. the used starting material of the present invention are each seed amino acid, all are natural biomaterials, and nontoxicity has no side effect, and are a kind of pharmaceutical carrier of environmental type and brand-new genophore, and the user is easy to accept.7. this invention preparation technology is simple, and equipment requirements is not high, easy handling, and also material is easy to get, and with low cost.
Description of drawings
Fig. 1 is hyperbranched polyamino acid of the present invention (Lys)
0.85-(Arg)
0.15(Lys)
0.7-(Arg)
0.3Load the design sketch that luciferase plasmids DNA leads at the 293T transit cell, its result shows hyperbranched polyamino acid of the present invention (Lys)
0.85-(Arg)
0.15(Lys)
0.7-(Arg)
0.3This gene of in the 293T cell, effectively transduceing.
Fig. 2 is hyperbranched polyamino acid of the present invention (Lys)
0.85-(Arg)
0.15(Lys)
0.7-(Arg)
0.3Load the design sketch that luciferase plasmids DNA leads at COS 7 transit cells, its result shows hyperbranched polyamino acid of the present invention (Lys)
0.85-(Arg)
0.15(Lys)
0.7-(Arg)
0.3This gene of in COS 7 cells, effectively transduceing.
Fig. 3 is hyperbranched polyamino acid of the present invention (Lys)
0.85-(Arg)
0.15(Lys)
0.7-(Arg)
0.3Load the design sketch that luciferase plasmids DNA leads at the HeLa transit cell, its result shows hyperbranched polyamino acid of the present invention (Lys)
0.85-(Arg)
0.15(Lys)
0.7-(Arg)
0.3This gene of in the HeLa cell, effectively transduceing.
Embodiment
Below in conjunction with embodiment the present invention is described in detail, but is not limited to the disclosed content of embodiment.
Embodiment 1:(Lys)
0.9-(Arg)
0.1Synthetic
With 60.0mmolL-Methionin (Lys) and 60.0mmolL-arginine (Arg) in mortar behind the mixing; the white solid mixture is moved in the 250ml there-necked flask; under argon shield and churned mechanically condition, reacting by heating mixture to 160 ℃ reaction 48 hours obtains yellow solid.Add 200ml methyl alcohol, the most of solid of ultrasonic dissolution.Filter, in filtrate, dropwise add tetrahydrofuran (THF), fractionation precipitation, obtain Methionin and arginic copolymerization product, the content that is recorded carbon atom in the product by elemental microanalysis method is 44.26%, and the content of nitrogen-atoms is 18.81%, the content of hydrogen atom is 7.84%, through determining that final product is (Lys)
0.9-(Arg)
0. 1, it is 1.5 * 10 that this product records its molecular weight Mw by gel permeation chromatography
4G/mol.
Embodiment 2:(Lys)
0.8-(Arg)
0.2Synthetic
The mixing in mortar 60.0mmol L lysine HCL and 60.0mmol potassium hydroxide; grind to form pulpous state; again to wherein adding 120.0mmol L-arginine; after mixing; the white solid mixture is moved in the 250ml there-necked flask; under argon shield and churned mechanically condition, reacting by heating mixture to 160 ℃ reaction 48 hours obtains yellow solid.Add 200ml methyl alcohol, the most of solid of ultrasonic dissolution.Filter, in filtrate, dropwise add tetrahydrofuran (THF), fractionation precipitation, obtain Methionin and arginic copolymerization product, the content that is recorded carbon atom in the product by elemental microanalysis method is 45.05%, and the content of nitrogen-atoms is 20.10%, the content of hydrogen atom is 7.92%, through determining that final product is (Lys)
0.8-(Arg)
0.2, it is 1.1 * 10 that this product records its molecular weight Mw by gel permeation chromatography
4G/mol.
Embodiment 3:(Lys)
0.85-(His)
0.15Synthetic
With 60.0mmol L-Methionin and 50.0mmol L-Histidine in mortar behind the mixing; the white solid mixture is moved in the 250ml there-necked flask; under argon shield and churned mechanically condition, reacting by heating mixture to 120 ℃ reaction 64 hours obtains yellow solid.Add 150ml methyl alcohol, the most of solid of ultrasonic dissolution.Filter, in filtrate, dropwise add tetrahydrofuran (THF), fractionation precipitation, obtain the copolymerization product of Methionin and Histidine, the content that is recorded carbon atom in the product by elemental microanalysis method is 44.73%, and the content of nitrogen-atoms is 19.19%, the content of hydrogen atom is 7.34%, through determining that final product is (Lys)
0.85-(His)
0.15, it is 9.6 * 10 that this product records its molecular weight Mw by gel permeation chromatography
3G/mol.
Embodiment 4:(Lys)
0.6-(His)
0.4Synthetic
The mixing in mortar with 60.0mmol L lysine HCL and 60.0mmol potassium hydroxide; grind to form pulpous state; again to wherein adding 150.0mmol L-Histidine in mortar behind the mixing; the white solid mixture is moved in the 250ml there-necked flask; under argon shield and churned mechanically condition; reacting by heating mixture to 160 ℃ reaction 48 hours obtains yellow solid.Add 200ml methyl alcohol, the most of solid of ultrasonic dissolution.Filter, in filtrate, dropwise add tetrahydrofuran (THF), fractionation precipitation, obtain the copolymerization product of Methionin and Histidine, the content that is recorded carbon atom in the product by elemental microanalysis method is 45.75%, and the content of nitrogen-atoms is 21.46%, the content of hydrogen atom is 6.25%, through determining that final product is (Lys)
0.6-(His)
0.4, it is 6.8 * 10 that this product records its molecular weight Mw by gel permeation chromatography
3G/mol.
Embodiment 5:(Lys)
0.75-(Arg)
0.15-(His)
0.1Synthetic
With 60.0mmol L-Methionin; 50.0mmol L-arginine and 45.0mmol L-Histidine are in mortar behind the mixing; the white solid mixture is moved in the 250ml there-necked flask; under argon shield and churned mechanically condition; reacting by heating mixture to 160 ℃ reaction 56 hours obtains yellow solid.Add 200ml methyl alcohol, the most of solid of ultrasonic dissolution.Filter, in filtrate, dropwise add tetrahydrofuran (THF), fractionation precipitation, obtain the copolymerization product of Methionin, arginine and Histidine, the content that is recorded carbon atom in the product by elemental microanalysis method is 45.13%, and the content of nitrogen-atoms is 20.07%, and the content of hydrogen atom is 7.69%, through determining that final product is (Lys)
0.75-(Arg)
0.15-(His)
0.1, it is 1.4 * 10 that this product records its molecular weight Mw by gel permeation chromatography
4G/mol.
Embodiment 6:(Lys)
0.65-(Arg)
0.1-(His)
0.1-(Ala)
0.15Synthetic
With 60.0mmol L-Methionin; 40.0mmol L-arginine; 50.0mmol L-Histidine and 80.0mmol L-L-Ala are in mortar behind the mixing; the white solid mixture is moved in the 250ml there-necked flask; under argon shield and churned mechanically condition; reacting by heating mixture to 140 ℃ reaction 60 hours obtains yellow solid.Add 200ml methyl alcohol, the most of solid of ultrasonic dissolution.Filter, in filtrate, dropwise add tetrahydrofuran (THF), fractionation precipitation, obtain the copolymerization product of Methionin, arginine, Histidine and L-Ala, the content that is recorded carbon atom in the product by elemental microanalysis method is 45.4%, and the content of nitrogen-atoms is 19.35%, and the content of hydrogen atom is 7.57%, through determining that final product is (Lys)
0.65-(Arg)
0.1-(His)
0.1-(Ala)
0.15, it is 1.2 * 10 that this product records its molecular weight Mw by gel permeation chromatography
4G/mol.
Embodiment 7:(Lys)
0.55-(Arg)
0.2-(His)
0.15-(Gln)
0.1Synthetic
With 60.0mmol L-Methionin; 100.0mmol L-arginine; 80.0mmol L-Histidine and 40.0mmol L-glutaminate are in mortar behind the mixing; the white solid mixture is moved in the 250ml there-necked flask; under argon shield and churned mechanically condition; reacting by heating mixture to 140 ℃ reaction 60 hours obtains yellow solid.Add 200ml methyl alcohol, the most of solid of ultrasonic dissolution.Filter, in filtrate, dropwise add tetrahydrofuran (THF), fractionation precipitation, obtain the copolymerization product of Methionin, arginine, Histidine and glutamine, the content that is recorded carbon atom in the product by elemental microanalysis method is 43.06%, and the content of nitrogen-atoms is 20.74%, and the content of hydrogen atom is 7.13%, through determining that final product is (Lys)
0.65-(Arg)
0.1-(His)
0.1-(Ala)
0.15, it is 1.6 * 10 that this product records its molecular weight Mw by gel permeation chromatography
4G/mol.
Embodiment 8:(Lys)
0.7-(Arg)
0.2-(Phe)
0.1Synthetic
With 60.0mmol L-Methionin; 90.0mmol L-arginine and 40.0mmol L-phenylalanine are in mortar behind the mixing; the white solid mixture is moved in the 250ml there-necked flask; under argon shield and churned mechanically condition; reacting by heating mixture to 160 ℃ reaction 45 hours obtains yellow solid.Add 200ml methyl alcohol, the most of solid of ultrasonic dissolution.Filter, in filtrate, dropwise add tetrahydrofuran (THF), fractionation precipitation, obtain the copolymerization product of Methionin, arginine and phenylalanine, the content that is recorded carbon atom in the product by elemental microanalysis method is 46.38%, and the content of nitrogen-atoms is 18.66%, and the content of hydrogen atom is 7.72%, through determining that final product is (Lys)
0.7-(Arg)
0.2-(Phe)
0.1, it is 1.25 * 10 that this product records its molecular weight Mw by gel permeation chromatography
4G/mol.
Embodiment 9:
Hyperbranched polyamino acid non-viral gene vector with embodiment 1～8 preparation, adopt GelRed as the DNA luminescent dye molecule respectively, compound afterwards with its binding ability of gel electrophoresis therapy determining by different N/P ratios respectively with DNA hyperbranched polyamino acid, measurement result shows: all effectively association of inducing DNA molecule of genophore of pressing embodiment 1～8 preparation.
Embodiment 10:
Press the hyperbranched polyamino acid non-viral gene vector of embodiment 1 and embodiment 2 preparations, difference external transduction 293T, COS 7 and HeLa cell, after the transfection 4 hours, with the expression of luciferase detection system test luciferase reporter gene in above three kinds of cells, its result is shown in accompanying drawing 1,2,3.The result shows: this hyperbranched polyamino acid non-viral gene vector (Lys)
0.85-(Arg)
0.15(Lys)
0.7-(Arg)
0.3These three kinds of cells all there is very high transduction efficiency.
Embodiment 11:
Press the hyperbranched polyamino acid non-viral gene vector of embodiment 3～8 preparation, external transduction HEK293 cell respectively, transfection is after 36 hours, the expression of fluorescence microscope green fluorescent protein.The result shows: hyperbranched polyamino acid non-viral gene vector this cell of effectively transduceing.
Embodiment 12:
Press the hyperbranched polyamino acid non-viral gene vector of embodiment 1 and embodiment 2 preparations, the external transduction rice callus histocyte of difference, transfection is after 48 hours, and fluorescence microscope obtains expressing in paddy rice wound healing tissue cell to green fluorescent protein.
Claims (5)
1. hyperbranched polyamino acid is characterized in that its chemical constitution has following general formula:
Lys, Arg, His are respectively Methionin, arginine, Histidine in the formula, and X is any or several seed amino acids except that above-mentioned amino acid, wherein a, b, c, d are molar fraction, 0.2≤a≤0.95,0≤b≤0.8,0≤c≤0.8,0≤d≤0.3, and a+b+c+d=1.
2. the preparation method of the described hyperbranched polyamino acid of claim 1, after comprising the steps: that other amino acid of containing in the chemical constitution with Methionin or lysine salt and the described hyperbranched polyamino acid of claim 1 or its amino acid salts mix, obtain yellow solid 130～180 ℃ of reactions after 2～64 hours, this thick product obtains hyperbranched polyamino acid behind precipitator method purifying; The mol ratio of other amino acid of any that contains in the chemical constitution of Methionin or lysine salt and the described hyperbranched polyamino acid of claim 1 or its amino acid salts is 1: 0～20, and amino acid or its amino acid salts raw material consumption that b, c in the chemical constitution of 1: 0 described hyperbranched polyamino acid of expression claim 1 wherein or d are 0 o'clock correspondence are 0.
3. claim 1 or 2 described hyperbranched polyamino acids are as the application of genophore.
4. application according to claim 3 is characterized in that: described genophore is the carrier that is used for human body or zooblast gene transfer.
5. application according to claim 3 is characterized in that: described genophore is the carrier that is used for the vegetable cell gene transfer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100627021A CN101575412B (en) | 2009-06-12 | 2009-06-12 | Hyperbranched polyamino acid, preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100627021A CN101575412B (en) | 2009-06-12 | 2009-06-12 | Hyperbranched polyamino acid, preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101575412A true CN101575412A (en) | 2009-11-11 |
| CN101575412B CN101575412B (en) | 2011-05-11 |
Family
ID=41270498
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100627021A Expired - Fee Related CN101575412B (en) | 2009-06-12 | 2009-06-12 | Hyperbranched polyamino acid, preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101575412B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104316679A (en) * | 2014-10-29 | 2015-01-28 | 南京基蛋生物科技有限公司 | Application of hyperbranched polyglycerol modified magnetic nanoparticle microspheres in chemiluminescence immune assay |
| CN104535761A (en) * | 2014-12-18 | 2015-04-22 | 基蛋生物科技股份有限公司 | Hyperbranched polyglycerol modified latex microsphere enhanced immunoturbidimetry and application thereof |
| CN108184852A (en) * | 2018-01-31 | 2018-06-22 | 中国科学院长春应用化学研究所 | A kind of polyaminoacid bacteriostatic agent and application |
| CN108276572A (en) * | 2018-01-31 | 2018-07-13 | 中国科学院长春应用化学研究所 | A kind of branched polyaminoacid bacteriostatic agent and application |
| WO2019149121A1 (en) * | 2018-01-31 | 2019-08-08 | 中国科学院长春应用化学研究所 | Branched polyamino acid bacteriostatic agent and application thereof |
| CN115040659A (en) * | 2022-05-30 | 2022-09-13 | 浙江大学 | Nontoxic polycation high polymer carrier material |
| CN115068680A (en) * | 2022-05-30 | 2022-09-20 | 浙江大学 | Tissue regeneration promoting material with self-adaptability |
| CN115109801A (en) * | 2022-08-25 | 2022-09-27 | 深圳市先康达生命科学有限公司 | Slow virus transfection transfer aid and application thereof |
-
2009
- 2009-06-12 CN CN2009100627021A patent/CN101575412B/en not_active Expired - Fee Related
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104316679A (en) * | 2014-10-29 | 2015-01-28 | 南京基蛋生物科技有限公司 | Application of hyperbranched polyglycerol modified magnetic nanoparticle microspheres in chemiluminescence immune assay |
| CN104316679B (en) * | 2014-10-29 | 2016-04-06 | 基蛋生物科技股份有限公司 | The application of hyperbranched polyglycidyl ether decorated nanometer magnetic microsphere in chemiluminescence immune assay |
| CN104535761A (en) * | 2014-12-18 | 2015-04-22 | 基蛋生物科技股份有限公司 | Hyperbranched polyglycerol modified latex microsphere enhanced immunoturbidimetry and application thereof |
| KR20200116134A (en) * | 2018-01-31 | 2020-10-08 | 창춘 인스티튜트 오브 어플라이드 케미스트리, 차이니즈 아카데미 오브 사이언스 | Branched poly (amino acid) antimicrobial agents and uses thereof |
| CN108276572A (en) * | 2018-01-31 | 2018-07-13 | 中国科学院长春应用化学研究所 | A kind of branched polyaminoacid bacteriostatic agent and application |
| WO2019149121A1 (en) * | 2018-01-31 | 2019-08-08 | 中国科学院长春应用化学研究所 | Branched polyamino acid bacteriostatic agent and application thereof |
| CN108184852A (en) * | 2018-01-31 | 2018-06-22 | 中国科学院长春应用化学研究所 | A kind of polyaminoacid bacteriostatic agent and application |
| EP3747932A4 (en) * | 2018-01-31 | 2021-10-27 | Changchun Institute of Applied Chemistry, Chinese Academy of Sciences | Branched polyamino acid bacteriostatic agent and application thereof |
| CN113621135A (en) * | 2018-01-31 | 2021-11-09 | 中国科学院长春应用化学研究所 | Branched polyamino acid bacteriostatic agent and application thereof |
| KR102541633B1 (en) | 2018-01-31 | 2023-06-12 | 창춘 인스티튜트 오브 어플라이드 케미스트리, 차이니즈 아카데미 오브 사이언스 | Branched polyamino acid antimicrobial agents and uses thereof |
| CN115040659A (en) * | 2022-05-30 | 2022-09-13 | 浙江大学 | Nontoxic polycation high polymer carrier material |
| CN115068680A (en) * | 2022-05-30 | 2022-09-20 | 浙江大学 | Tissue regeneration promoting material with self-adaptability |
| WO2023231048A1 (en) * | 2022-05-30 | 2023-12-07 | 浙江大学 | Non-toxic polycation polymer carrier material |
| CN115109801A (en) * | 2022-08-25 | 2022-09-27 | 深圳市先康达生命科学有限公司 | Slow virus transfection transfer aid and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101575412B (en) | 2011-05-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101575412B (en) | Hyperbranched polyamino acid, preparation method and application thereof | |
| Scholl et al. | Dendritic and hyperbranched polyamides | |
| Kim et al. | Arginine-conjugated polypropylenimine dendrimer as a non-toxic and efficient gene delivery carrier | |
| Smith et al. | Synthetic peptide-based DNA complexes for nonviral gene delivery | |
| Ohsaki et al. | In vitro gene transfection using dendritic poly (L-lysine) | |
| Zugates et al. | Synthesis of poly (β-amino ester) s with thiol-reactive side chains for DNA delivery | |
| CN102256999B (en) | To leukocytic effective transhipment | |
| US20180028455A1 (en) | Peptide/particle delivery systems | |
| He et al. | Defined polymeric materials for gene delivery | |
| Obeid et al. | Synthesis and self-assembly of well-defined poly (amino acid) end-capped poly (ethylene glycol) and poly (2-methyl-2-oxazoline) | |
| Kumar et al. | Side-chain amino-acid-based ph-responsive self-assembled block copolymers for drug delivery and gene transfer | |
| CN101597349A (en) | Phenyloboricacid-modified cationic polymer and synthetic method thereof and application | |
| Bauer et al. | Secondary structure-driven self-assembly of thiol-reactive polypept (o) ides | |
| WO2006090924A1 (en) | Block copolymer having peptide ligand | |
| Pan et al. | Short multi-armed polylysine-graft-polyamidoamine copolymer as efficient gene vectors | |
| CN109355310A (en) | ROS (reactive oxygen species) -responsive gene delivery vector as well as preparation method and application thereof | |
| CN110478322A (en) | A kind of nucleic acid drug compound and its preparation method and application | |
| Liu et al. | Thermoresponsive polypeptoids | |
| Li et al. | Branch unit distribution matters for gene delivery | |
| Cheng et al. | Thermo-sensitive mPEG-PA-PLL hydrogel for drug release of calcitonin | |
| Cheng et al. | Novel thermoresponsive nonviral gene vector: P (NIPAAm-co-NDAPM)-b-PEI with adjustable gene transfection efficiency | |
| CA2377211A1 (en) | Copolymers for transporting nucleic acids in the cell | |
| CN105418939B (en) | The high molecular material of guanidine radicals substituted aromatic modification, preparation method and application | |
| Du et al. | Azo-capped polysarcosine-b-polylysine as polypeptide gene vector: a new strategy to improve stability and easy optimization via host–guest interaction | |
| Annenkov et al. | Design of oligonucleotide carriers: importance of polyamine chain length |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Jiangsu Cheng Yi Pharmaceutical Co., Ltd. Assignor: Wuhan University Contract record no.: 2012320000687 Denomination of invention: Hyperbranched polyamino acid, preparation method and application thereof Granted publication date: 20110511 License type: Exclusive License Open date: 20091111 Record date: 20120531 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110511 Termination date: 20160612 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |