CN102115498A - Connexin core sequence-containing amphiphilic polypeptide and application thereof - Google Patents
Connexin core sequence-containing amphiphilic polypeptide and application thereof Download PDFInfo
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- CN102115498A CN102115498A CN2009102734935A CN200910273493A CN102115498A CN 102115498 A CN102115498 A CN 102115498A CN 2009102734935 A CN2009102734935 A CN 2009102734935A CN 200910273493 A CN200910273493 A CN 200910273493A CN 102115498 A CN102115498 A CN 102115498A
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Abstract
The invention provides connexin core sequence-containing amphiphilic polypeptide AcN-RADARADARADARADAGGDHLSDNYTLDHDRAIH-CONH2, wherein the amphiphilic polypeptide and the amphiphilic polypeptide with the structure of AcN-RADARADARADARADA-CONH2 are triggered by Ca2+or a cell culture medium DMEM-F12 to automatically form into a compound, i.e. a nanometer-grade fiber material, and the nanometer-grade fiber material is taken as a bracket of the bone mesenchymal stem cells, so that the biological behavior of the cells can be obviously improved, the degenerated intervertebral disc can be repaired, and the original height can be recovered.
Description
Technical field:
The invention belongs to medical science and biotechnology, relate to and contain the amphipathic polypeptide that connects the protein core sequence and the application in medical science thereof.
Background technology:
Intervertebral disc degeneration (IVD) is to cause the low back pain most important reason, studies show that the people of 60%-80% to I haven't seen you for ages a low back pain takes place in life at it.Intervertebral disc degeneration mainly shows as the nucleus pulposus water content to be reduced, and the tension force of nucleus pulposus is descended, and disc height descends.Simultaneously, hyaluronic acid and angling vitriol reduce, and low-molecular-weight glycoprotein increases, and protofibril sex change and collegen filament deposition increase, and nucleus pulposus follows the string, and intervertebral disc structure is lax.Thereby this regression in case take place will be absorbed in the regression that a kind of vicious cycle further increases the weight of intervertebral disk causes lumbago and skelalgia.The regression that how to prevent intervertebral disc degeneration and reverse intervertebral disk is the problem that the treatment intervertebral disc degeneration presses for solution.
The method of traditional treatment intervertebral disc degeneration mainly is an operative treatment, but its late result is unsatisfactory, because can cause the regression of adjacent discs and the formation of adjacent vertebral spur after the operation.In recent years, the treatment intervertebral disc degeneration that develops into of organizational project has brought new thinking, and wherein biologic bracket material has been brought into play important effect in the disc tissue engineering.Traditional timbering material such as chitosan, hyaluronic acid, scleroproein, collagen derivative etc., although the effect of certain promotion cell adhesion, growth and differentiation is arranged, but its ubiquity physical strength height, biological degradability are poor, degradation product has toxicity, biological activity difference and has shortcomings such as immunogenicity, have limited it in the disc tissue application in engineering.
Given this, we provide a kind of can address the above problem can to treat the nano-fiber material support of intervertebral disc degeneration as repair vector real in necessary.
Summary of the invention
The object of the present invention is to provide a kind of amphipathic polypeptide DHL-PA that connects the protein core sequence that contains, utilizes this amphipathic polypeptide to prepare a kind of nanometer stage material, make this nanometer stage material can be as the timbering material of reparation regression intervertebral disk.
Realize that technical scheme of the present invention is:
Provided by the invention to contain the amphipathic amino acid sequence of polypeptide that connects the protein core sequence be RADARADARADARADAGGDHLSDNYTLDHDRAIH (seeing sequence 3 in the sequence table), and it is that the connection protein core sequence linkN (seeing sequence 1 in the sequence table) of DHLSDNYTLDHDRAIH and RADA-16 (seeing sequence 2 in the sequence table) and spatial spread amino acid-GG-that aminoacid sequence is RADARADARADARADA form by aminoacid sequence.Consider polypeptide degraded easily itself; the present invention carries out acetylize (AcN-) and amidation respectively at the aminoterminal that contains the amphipathic polypeptide RADARADARADARADAGGDHLSDNYTLDHDRAIH that connects the protein core sequence and carboxyl terminal, and (CONH2) processing, obtaining structure is AcN-RADARADARADARADAGGDHLSDNYTLDHDRAIH-CONH
2Amphipathic polypeptide.
Nanometer stage material provided by the invention is to be AcN-RADARADARADARADAGGDHLSDNYTLDHDRAIH-CONH by structure
2(DHL-PA) amphipathic polypeptide and structure are AcN-RADARADARADARADA-CONH
2(RADA-16-PA) amphipathic polypeptide is at Ca
2+Or cell culture medium DMEM-F12 triggers the mixture (DHL-PA/RADA-16-PA) that self-assembly down forms.This nano-fiber material can obviously improve the biological behaviour of cell as the support of mesenchymal stem cells MSCs, is used to repair the intervertebral disk of regression, makes it recover original height.This timbering material is used for the disc tissue engineering, and is safe and effective, and its side effect is little, may become the most promising timbering material in disc tissue engineering aspect.
Connect protein core sequence linkN and (DHLSDNYTLDHDRAIH-) be selected from the U.S. medline gene pool and the document that sees reference: Mwale F, Demers CN, Petit A, et al.A synthetic peptideof link protein stimulates the biosynthesis of collagens II, IX andproteoglycan by cells of the intervertebral disc.J Cell Biochem, 2003; 88 (6): 1202-1213.
LinkN connects proteic core sequence in the nucleus pulposus cell epimatrix, structure of its pair cell epimatrix and nucleus pulposus inner cell have the regulating effect of very important uniqueness.The function of linkN has: 1. as connecting the protein active polypeptide segment, participate in stablizing aggrecan and hyaluronic non-covalent the connection, protected protein polysaccharide polymer prevents its degraded in the regression process.Because aggrecan is the maximum composition of content in the protein-polysaccharide, its degraded is one of nucleus pulposus regression performance the earliest, and caused the nucleus pulposus water content to descend thus and lose its physiological function, so link N is bringing into play important effect in the integrity of keeping the extracellular matrix 26S Proteasome Structure and Function.After link N polypeptide material is expelled to nucleus pulposus, will be by bringing into play the Stability Analysis of Structures effect at once with hyaluronic non-covalent the connection.2. linkN is a regulatory factor in the cell, the effect of analog growth factor is arranged, can directly act on the nucleus pulposus inner cell, stimulate and produce new extracellular matrix, promote the synthetic of protein-polysaccharide and II, IX Collagen Type VI and assemble, reverse that the II Collagen Type VI is transformed into type i collagen and proteoglycan content downward trend in the regression nucleus pulposus.3. inflammatory reaction is the important undesirable element that causes the extracellular matrix metabolic imbalance, link N can be by removing free radical, the degraded that slows down intervertebral disk inner cell epimatrix that inflammatory reaction causes is [referring to Mwale F, Demers CN, Petit A, et al.A synthetic peptide oflink protein stimulates the biosynthesis of collagens II, IX and proteoglycan by cells of theintervertebral disc.J Cell Biochem, 2003; 88 (6): 1202-1213; With Rodriguez E, Roughley P.Linkprotein can retard the degradation of hyaluronan in proteoglycan aggregates.OsteoarthritisCartilage, 2006; 14 (8): 823-829].So link N has protection simultaneously, stimulates synthetic new extracellular matrix and carries out constitutionally stable Trinitarian function, be unique active polypeptide in the nucleus pulposus cell epimatrix of finding at present with this function.
RADA-16 develops (arginine-L-Ala-aspartic acid-L-Ala-arginine-L-Ala-aspartic acid-L-Ala-arginine-L-Ala-aspartic acid-L-Ala-arginine-L-Ala-aspartic acid-L-Ala) [referring to Holmes TC from the EAKA16-II fragment of zuotin yeast protein, De Lacalle S, Su X, et al.Extensive meurite outgrowth and activesunapse formation onself-assembling peptide scaffolds.PNAS, 2000,97:6728-6733.].Among the RADA-16 because arginine, aspartic acid are polare Aminosaeren, solvability is good, and arginine has positive charge, aspartic acid has negative charge, so modify connection protein core sequence with RADA-16, the dissolving of synthetic polypeptide newly can be promoted on the one hand, the self-assembly of DHL-PA and RADA-16-PA can be promoted on the other hand.
Between linkN and the RADA-16-GG-can make the bioactive sequence linkN at rear portion that suitable space is arranged, be beneficial to the exposure of DHL-PA/RADA-16-PA avtive spot.In addition, consider polypeptide degraded easily itself, the present invention is at its aminoterminal and carboxyl terminal carries out acetylize (AcN-) respectively and amidation (CONH2) is handled DHL-PA (AcN-RADARADARADARADAGGDHLSDNYTLDHDRAIH-CONH of the present invention
2) amphipathic polypeptide, can adopt the solid-phase polypeptide automatic DNA synthesizer DNA to synthesize.The purity that high performance liquid chromatograph detects polypeptide is 97.02%, and it is 3730.92 that mass spectrograph detects its molecular weight.Detail parameters is seen Figure 10,11.
DHL-PA and RADA-16-PA are at Ca
2+Or cell culture medium DMEM-F12 can be self-assembled under triggering and be nano-fiber material (DHL-PA/RADA-16-PA), and it has and is similar to n cell epimatrix nanofibrous structures and good material-cell interface compatibility and biologic activity.The atomic power scanning electron microscope shows: the DHL-PA/RADA-16-PA nanofiber diameter is 38.9 ± 3.8nm, is similar to the fibrous texture (seeing Fig. 5,6) of n cell epimatrix nanometer (nm) yardstick.Cytotoxicity experiment illustrates that nano-fiber material of the present invention has good material-cell interface compatibility (seeing 6,7).The biologic activity test experience of material illustrates that nano-fiber material of the present invention has good biologic activity (Fig. 8,9).
Experimental data of the present invention
One, the synthetic and dissolving of polypeptide
Amphipathic polypeptide DHL-PA and RADA-16-PA entrust the synthetic and purifying of the biochemical company limited of Shanghai gill.
DHL-PA and each 10mg of RADA-16-PA are dissolved in respectively in the 100 μ l aseptic double-distilled waters, and concussion and with ultrasonication 30min (water-bath, 37 ℃) makes it fully dissolve formation achromaticity and clarification liquid, concentration be 10% (100mg/ml, m/v).
The self-assembly of two polypeptide and atomic force microscope detect
Getting dilution is 1% DHL-PA and the amphipathic polypeptide mixed solution 180 μ l of RADA-16-PA (volume ratio 1: 1), and placing volume is the microminiature tube of 1.5ml, adds Ca then gently
2+Cl
2180 μ l, 200 μ l valinche rifle heads are blown and beaten thorough mixing gently, and final concentration is 0.5%; Other gets the microminiature tube that the amphipathic polypeptide solution 180 μ l of RADA-16-PA place another equal volume, repeats aforesaid operations.2 microminiature tubes are put into 37.0 ℃ of incubator 30min, observe the self-assembly of polypeptide.See Fig. 2, illustrate that independent DHL-PA (B) is at Ca
2+Cl
2Triggering under can not be self-assembled into nanogel, DHL-PA and RADA-16-PA (C) are at Ca
2+Cl
2Triggering under can be self-assembled into nanogel jointly, DHL-PA and RADA-16-PA (D) can be self-assembled into nanogel jointly under the triggering of DMEM-F12.
With concentration is that the DHL-PA of 0.01% (m/v) and the amphipathic polypeptide mixed solution of RADA-16-PA (volume ratio 1: 1) or the simple amphipathic polypeptide solution 10 μ l of RADA-16-PA drip respectively gently in 2 agalmatolite sheet centers, respectively add DMEM-F12 cell culture medium 10 μ l then, wash gently 2 times with PBS behind the 30min, seasoning under the room temperature, atomic force microscope detects.See Fig. 4,5, afm scan shows: DHL-PA can not form nanofiber separately, and DHL-PA and RADA-16-PA can form nanofiber jointly.
Three peptide-based gel supports are to the influence of mesenchymal stem cells MSCs biological behaviour
Experiment purpose: observe the influence that the white assemble nanometer level of the present invention filamentary material DHL-PA/RADA-16-PA to rabbit bone marrow mesenchymal stem cell biological scholarship and moral conduct is.
Experiment material: cell culture medium DMEM-Fl2 (hyclone); Foetal calf serum (FBS, Gibco); Lymphocyte separation medium; Fluorexon/propidium iodide (sigma); CCK-8 test kit (the green skies); Inverted phase contrast microscope (Japan); Bechtop (Shanghai Boxun Industrial Co., Ltd.); CO
2Incubator (German Heraeus company); Fluorescent microscope (USA)
Experimental technique:
1 draw materials 3 age in week regular grade Japan large ear rabbit femur bone marrow, lymphocyte separation medium separation and purification mesenchymal stem cells MSCs and cultivate (37 ℃, 5% CO
2Concentration incubator, nutrient solution: DMEM-Fl2 and 10%FBS), with 3 generation purifying mesenchymal stem cells be used for subsequent experimental.
2 usefulness cell culture medium DMEM-Fl2 inspire amphipathic polypeptide solution makes it be self-assembled into nanogel, and this nanogel is as the growth support of mesenchymal stem cells MSCs.
3 are inoculated in the surface of above-mentioned gel with mesenchymal stem cells MSCs: 1. 0.5h, 2h, 4h, 6h, 8h are with the adhesion of CCK-8 indirect detection material pair cell.2. fluorexon after 7 days/propidium iodide dyeing, fluorescent microscope detects the biology toxicity of gel.3. CCK-8 reagent detects the proliferation activity of cell after 7 days.
Experimental result:
1. be 1: 1 blended DHL-PA (1% by volume, m/v) and RADA-16-PA (1%, m/v) amphipathic polypeptide mixed solution is self-assembled into nanometer stage material (being the nanogel support) under cell culture medium DMEM-F12 inspires, and the DHL-PA/RADA-16-PA nanofiber diameter obviously is coarser than simple RADA-16-PA nanofiber diameter.
2. DHL-PA/RADA-16-PA nanogel support and RADA-16-PA nanogel support are cultivated altogether with mesenchymal stem cells MSCs respectively and be there is no significant cytotoxicity after 7 days, and cell survival rate is all greater than 95%.
3. DHL-PA/RADA-16-PA nanogel support is compared with simple RADA-16-PA nanogel support, can obviously accelerate and improve the adhesion of cell.
4. the more simple RADA-16-PA nanogel support of DHL-PA/RADA-16-PA nanogel support has obviously promoted the propagation of mesenchymal stem cells MSCs.
Experiment conclusion: DHL-PA/RADA-16-PA and simple RADA-16-PA nanogel support all do not have significant cytotoxicity, but the more simple RADA-16-PA nanogel support of DHL-PA/RADA-16-PA nanogel support has obviously promoted the adhesion and the propagation of mesenchymal stem cells MSCs.
Description of drawings
Fig. 1: the aminoacid sequence of the amphipathic polypeptide DHL-PA of the present invention's design and the amphipathic peptide molecule of RADA-16-PA, DHL-PA constitute synoptic diagram (arrow is depicted as-G-G-amino acid among the figure)
Fig. 2: the sight substantially of gel: A) the amphipathic polypeptide solution of DHL-PA, B) the former bit inversion of A pipe, C) volume ratio is that 1: 1 blended DHL-PA and the amphipathic polypeptide mixed solution of RADA-16-PA are at Ca
2+Cl
2Triggering form down the DHL-PA/RADA-16-PA nanogel, D) volume ratio is that 1: 1 blended DHL-PA and the amphipathic polypeptide mixed solution of RADA-16-PA form the DHL-PA/RADA-16-PA nanogel under the triggering of DMEM-F12.
Fig. 3: show and trigger the DHL-PA/RADA-16-PA nanogel that forms in the particular circle model, illustrate that this gel has enough intensity.
Fig. 4 and Fig. 5: atomic force microscope images: DHL-PA can not form nanofiber separately; DHL-PA and RADA-16-PA can be self-assembled into nanofiber (Fibre diameter is 38.9 ± 3.8) jointly, are similar to the fibrous texture of n cell epimatrix nanometer (nm) yardstick and its water content greater than 99%.
Fig. 6 and Fig. 7: DHL-PA/RADA-16-PA, after the rice gel stent was cultivated 7 days altogether with mesenchymal stem cells MSCs in the RADA-16-PA, cell survival rate is (green shown in the arrow among the figure ↓ be viable cell, redness all greater than 95%
Be dead cell), the acellular toxicity of this nano-fiber material support is described.
Fig. 8: different stent materials is to the influence of mesenchymal stem cells MSCs adhesion property, the rice gel stent is compared with rice gel stent in the RADA-16-PA in the DHL-PA/RADA-16-PA, the former obviously accelerates and improves the adhesion (p＜0.01, difference has statistical significance) of cell.
Fig. 9: be the influence of different stent materials to mesenchymal stem cells MSCs propagation, DHL-PA/RADA-16-PA nanogel support is compared the propagation (P＜0.01, difference has statistical significance) that the former has obviously promoted cell with RADA-16-PA nanogel support.
Figure 10: high performance liquid chromatograph detects polypeptide purity, and it is 97.02% that high performance liquid chromatograph detects the purity that shows amphipathic polypeptide DHL-PA.
Figure 11: mass spectrograph detects amphipathic polypeptide DHL-PA molecular weight, and it is 3730.92 that mass spectrograph detects the molecular weight that shows amphipathic polypeptide DHL-PA.
Embodiment
Prepare nanometer stage material of the present invention
Nanometer stage material of the present invention is AcN-RADARADARADARADAGGDHLSDNYTLDHDRAIH-CONH by structure
2(DHL-PA) amphipathic polypeptide and structure are AcN-RADARADARADARADA-CONH
2(RADA-16-PA) amphipathic polypeptide self-assembly forms.
Adopt the synthetic DHL-PA (AcN-RADARADARADARADAGGDHLSDNYTLDHDRAIH-CONH of solid-phase polypeptide automatic DNA synthesizer DNA
2) amphipathic polypeptide, the purity that high performance liquid chromatograph detects polypeptide is 97.02%, and it is 3730.92 that mass spectrograph detects its molecular weight, and detail parameters is seen Figure 10,11.
With concentration be 0.25%-10% (m/v) DHL-PA and the amphipathic polypeptide solution of RADA-16-PA according to DHL-PA and (DHL-PA+RADA-16-PA) volume ratio be that the ratio of 10%-75% is at Ca
2+Carry out self-assembly under triggering and form composite nano-fiber material (DHL-PA/RADA-16-PA).This matrix material has good material-cell interface compatibility and biologic activity, is used for disc tissue engineering aspect.
This nano-fiber material has and is similar to n cell epimatrix nanofibrous structures and good material-cell interface compatibility and biologic activity.The atomic power scanning electron microscope shows: the DHL-PA/RADA-16-PA nanofiber diameter is 38.9 ± 3.8nm, is similar to the fibrous texture (seeing Fig. 5,6) of n cell epimatrix nanometer (nm) yardstick.Cytotoxicity experiment illustrates that nano-fiber material of the present invention has good material-cell interface compatibility (seeing Fig. 6,7).The biologic activity test experience of material illustrates that nano-fiber material of the present invention has good biologic activity (seeing Fig. 8,9).
Difference from Example 1 is: the trigger condition that the amphipathic polypeptide solution self-assembly of DHL-PA and RADA-16-PA forms composite nano-fiber material is: carry out self-assembly and form composite nano-fiber material under cell culture medium DMEM-F12 triggers.All the other are with embodiment 1.
Below amino acid whose sequence table for the present invention relates to, wherein: sequence 1 is: connect protein core sequence linkN; Sequence 2 is: come RADA-16 from the EAKA16-II fragment evolution of zuotin yeast protein; Sequence 3 is: the amphipathic polypeptide that connects the protein core sequence that contains provided by the invention.
Sequence table
＜110〉Wuhan Union Hospital
＜120〉contain amphipathic polypeptide and the application thereof that connects the protein core sequence
<130>/
<160>3
<170>PatentIn?version?3.3
<210>1
<211>16
<212>PRT
＜213〉mankind
<400>1
Asp?His?Leu?Ser?Asp?Asn?Tyr?Thr?Leu?Asp?His?Asp?Arg?Ala?Ile?His
1 5 10 15
<210>2
<211>16
<212>PRT
＜213〉artificial
<400>2
Arg?Ala?Asp?Ala?Arg?Ala?Asp?Ala?Arg?Ala?Asp?Ala?Arg?Ala?Asp?Ala
1 5 10 15
<210>3
<211>34
<212>PRT
＜213〉artificial
<400>3
Arg?Ala?Asp?Ala?Arg?Ala?Asp?Ala?Arg?Ala?Asp?Ala?Arg?Ala?Asp?Ala
1 5 10 15
Gly?Gly?Asp?His?Leu?Ser?Asp?Asn?Tyr?Thr?Leu?Asp?His?Asp?Arg?Ala
20 25 30
Ile?His
Claims (6)
1. contain the amphipathic polypeptide that connects the protein core sequence, it is characterized in that it has the sequence 3 described aminoacid sequences that show in the sequence table.
2. the amphipathic polypeptide that connects the protein core sequence that contains according to claim 1 is characterized in that, has carried out acetylize and amidation processing respectively at its aminoterminal and carboxyl terminal.
3. claim 1 or 2 describedly contains the amphipathic polypeptide that connects the protein core sequence is used for repairing the timbering material of regression intervertebral disk in preparation application.
4. a nanometer stage material is characterized in that, it is to be AcN-RADARADARADARADAGGDHLSDNYTLDHDRAIH-CONH by structure
2Amphipathic polypeptide and structure be AcN-RADARADARADARADA-CONH
2Amphipathic polypeptide at Ca
2+Or cell culture medium DMEM-F12 triggers the mixture that self-assembly down forms.
5. the described nanometer stage material of claim 4 is used for repairing the application of the timbering material of regression intervertebral disk in preparation.
6. the preparation method of a nanometer stage material is characterized in that, will be AcN-RADARADARADARADAGGDHLSDNYTLDHDRAIH-CONH by structure
2Amphipathic polypeptide and structure be AcN-RADARADARADARADA-CONH
2Amphipathic polypeptide at Ca
2+Or cell culture medium DMEM-F12 triggers the mixture that self-assembly down forms.
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| Publication Number | Publication Date |
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| CN102115498A true CN102115498A (en) | 2011-07-06 |
| CN102115498B CN102115498B (en) | 2013-11-06 |
Family
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102911258A (en) * | 2012-07-06 | 2013-02-06 | 江苏大学 | Method for forming two-dimensional polypeptide nanosheets by regulating assembly of polypeptides with organic micromolecules |
| CN104497107A (en) * | 2014-12-08 | 2015-04-08 | 重庆医科大学 | Self-assembling oligopeptide and application thereof in three-dimensional cell culture |
| CN104693277A (en) * | 2015-03-26 | 2015-06-10 | 罗忠礼 | Self-assembled oligopeptide and application of self-assembled oligopeptide in three-dimensional cell culture |
| CN105169474A (en) * | 2015-08-24 | 2015-12-23 | 暨南大学 | Polypeptide material capable of carrying out self-assembly to form hydrogel under neutral pH condition and applications thereof |
| CN111939323A (en) * | 2020-08-08 | 2020-11-17 | 武汉速普生物科技有限公司 | Functional polypeptide hydrogel containing hyaluronic acid connecting peptide and connecting protein terminal peptide and application thereof |
-
2009
- 2009-12-31 CN CN2009102734935A patent/CN102115498B/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| 邹枕玮: "自组装IKVAV多肽纳米支架及其对背根神经节神经元细胞的作用", 《中国脊柱脊髓杂志》 * |
| 郑琪 等: "骨组织工程纳米复合支架及其生物学评价", 《中国组织工程研究与临床》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102911258A (en) * | 2012-07-06 | 2013-02-06 | 江苏大学 | Method for forming two-dimensional polypeptide nanosheets by regulating assembly of polypeptides with organic micromolecules |
| CN102911258B (en) * | 2012-07-06 | 2014-07-30 | 江苏大学 | Method for forming two-dimensional polypeptide nanosheets by regulating assembly of polypeptides with organic micromolecules |
| CN104497107A (en) * | 2014-12-08 | 2015-04-08 | 重庆医科大学 | Self-assembling oligopeptide and application thereof in three-dimensional cell culture |
| CN104497107B (en) * | 2014-12-08 | 2017-09-19 | 重庆医科大学 | A kind of self-assembled short peptide and its application in three-dimensional cell cultivation |
| CN104693277A (en) * | 2015-03-26 | 2015-06-10 | 罗忠礼 | Self-assembled oligopeptide and application of self-assembled oligopeptide in three-dimensional cell culture |
| CN104693277B (en) * | 2015-03-26 | 2018-02-13 | 罗忠礼 | A kind of self-assembled short peptide and its application in three-dimensional cell cultivation |
| CN105169474A (en) * | 2015-08-24 | 2015-12-23 | 暨南大学 | Polypeptide material capable of carrying out self-assembly to form hydrogel under neutral pH condition and applications thereof |
| CN111939323A (en) * | 2020-08-08 | 2020-11-17 | 武汉速普生物科技有限公司 | Functional polypeptide hydrogel containing hyaluronic acid connecting peptide and connecting protein terminal peptide and application thereof |
| CN111939323B (en) * | 2020-08-08 | 2022-06-10 | 武汉速普生物科技有限公司 | Functional polypeptide hydrogel containing hyaluronic acid connecting peptide and connecting protein terminal peptide and application thereof |
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| Publication number | Publication date |
|---|---|
| CN102115498B (en) | 2013-11-06 |
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