CN114409761A - Transforming growth factor beta1 active polypeptide and application thereof - Google Patents
Transforming growth factor beta1 active polypeptide and application thereof Download PDFInfo
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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Abstract
The invention discloses a transforming growth factor beta1 active polypeptide and application thereof, belonging to the technical field of transforming growth factor beta1 active polypeptide. The amino acid sequence of the transforming growth factor beta1 active polypeptide is shown in SEQ ID NO. 23. The invention also discloses application of the transforming growth factor beta1 active polypeptide in preparing a medicament for treating wound healing. The invention screens TGF-beta 1 key sequence by using phage random dodecapeptide library to synthesize TGF-beta 1 active polypeptide in vitro, which can be synthesized in large quantity in a short time and greatly reduce the production cost.
Description
Technical Field
The invention relates to a transforming growth factor beta1 active polypeptide and application thereof, belonging to the technical field of transforming growth factor beta1 active polypeptide.
Background
Wound healing is a complex process requiring multiple cells, extracellular matrix and signaling pathways to coordinate and participate in tissue defect repair. At present, refractory wounds such as chronic wounds of diabetes mellitus are difficult to solve clinically. The local application of growth factors can promote wound healing, but the currently applied growth factor products have complex production process, high economic cost, short biological half-life period and poor stability, are difficult to achieve the expected treatment effect, and greatly limit the clinical application of the growth factors.
At present, the research and application of the polypeptide reach the unprecedented prosperous degree. Compared with natural protein, the polypeptide has the advantages of good stability, good solubility, no need of animal carrier production, no immunogenicity, and mass production in vitro. Phage random peptide Library (Phage Library) is a Phage aggregate displaying various exogenous polypeptides with specific length, and has been widely applied to the aspects of antigen epitope simulation, protein engineering modification and the like.
Transforming growth factor beta1 (TGF-beta 1) is an important factor for promoting wound healing, and can promote fibroblast proliferation, enhance collagen formation and deposition, regulate extracellular matrix balance, and promote transdifferentiation of fibroblasts into myofibroblasts. However, at present, no report about the application of transforming growth factor beta1 in preparing active polypeptide gel exists.
In view of the above, there is a need to provide transforming growth factor β 1 and its application to solve the deficiencies of the prior art.
Disclosure of Invention
One of the purposes of the invention is to provide a transforming growth factor beta1 active polypeptide.
The technical scheme for solving the technical problems is as follows: the amino acid sequence of the transforming growth factor beta1 active polypeptide is shown in SEQ ID NO. 23.
HQKQQLQGVNVCGGRCCHGWSKAPGSQRCT(SEQ ID NO.23)。
The transforming growth factor beta1 active polypeptide of the invention has the following beneficial effects:
1. the invention uses the phage dodecapeptide library to screen TGF-beta 1 key sequences, carries out in vitro synthesis of TGF-beta 1 active polypeptides, improves the production efficiency and greatly reduces the production cost.
2. The invention can adjust the sequence structure of the peptide chain, modify the peptide chain and improve the space conformation and stability of the active polypeptide; and the generation does not need to use an animal carrier, has no immunogenicity, avoids the spread of diseases and avoids the ethical problem. Thus, the defects of poor stability, high cost, easy degradation and the like of the traditional growth factor are overcome, and the method has better stability, immunogenicity and safety.
The second object of the present invention is to provide the use of the above-mentioned transforming growth factor beta1 active polypeptide.
The technical scheme for solving the technical problems is as follows: the transforming growth factor beta1 active polypeptide is applied to preparing the medicine for treating wound healing.
The transforming growth factor beta1 active polypeptide has the following beneficial effects:
the transforming growth factor beta1 active polypeptide can be used for preparing a medicament for treating wound healing, can promote wound healing, effectively reduce inflammation, improve healing efficiency and effect, and has no toxic or side effect on a human body.
On the basis of the technical scheme, the invention can be further improved as follows.
Furthermore, the medicine for treating wound healing comprises an effective amount of transforming growth factor beta1 active polypeptide and pharmaceutically acceptable auxiliary materials.
The adoption of the further beneficial effects is as follows: the medicine for treating wound healing adopts the components, can effectively treat wound healing, has obvious treatment effect and small toxic and side effects.
Furthermore, the medicament for treating wound healing is in any one of a semi-solid preparation for external use, a solid preparation for external use and a liquid preparation for external use.
The further beneficial effects of the adoption are as follows: the preparation type is more convenient for patients to use.
Further, the semisolid preparation for external use is a paste.
Further, the ointment is a gel or an emulsion.
The further beneficial effects of the adoption are as follows: the gel or the emulsion is adopted, the defects of poor stability, high cost, easy degradation and the like of the traditional growth factor are overcome, the wound healing promoting effect is achieved, and the gel or the emulsion can be used for preparing medicines for healing diabetic chronic wounds, superficial burns, partial cortex burns, skin supply area wounds, postoperative wounds, skin bruises and other wounds.
Furthermore, the gel consists of transforming growth factor beta1 active polypeptide and a matrix, wherein the dosage of the transforming growth factor beta1 active polypeptide is 2000 IU/g gel matrix to 10000 IU/g gel matrix.
The further beneficial effects of the adoption are as follows: by adopting the dosage, higher cure rate and ideal curative effect can be achieved.
Further, the dose of the transforming growth factor beta1 active polypeptide is 8000 IU/g of gel matrix.
The further beneficial effects of the adoption are as follows: by adopting the dosage, higher cure rate and ideal curative effect can be achieved.
Still further, the gel matrix comprises a mixture of poloxamer 407, carbomer, methylparaben, and heparin.
The further beneficial effects of the adoption are as follows: in the gel, the bergamot 407 is used as the main component of the gel matrix, carbomer is used as a humectant, methylparaben is used as a preservative, and heparin sodium is used as a stabilizer.
Detailed Description
The principles and features of this invention are described below in conjunction with specific embodiments, which are set forth merely to illustrate the invention and are not intended to limit the scope of the invention.
Example 1: screening of TGF-beta 1 active polypeptide sequence
A96-well plate is coated with a human TGF-beta 1 monoclonal antibody, a phage random dodecapeptide library (purchased from NEB company, USA) is added for incubation at 4 ℃ overnight, the plate is washed 10 times by TBST, bound phage are eluted by an elution buffer (0.2mol/L of Glycine-HCl, pH 2.2, 0.1% BSA), and the eluate is rapidly neutralized by a neutralization buffer (1mol/L of Tris-HCl, pH 9.1).
Coli ER2738 host bacteria were used to amplify the eluate for the next round of screening. The same process was followed by three additional rounds of screening of the eluate from each round. Performing titer determination on eluate of the fourth round, randomly selecting phage blue spot, amplifying, and adjusting to 2.0 × 1013pfu/mL。
The binding force of monoclonal phage was detected using ELISA and human TGF-. beta.1 immunoassay kit (purchased from R & D, USA) according to the kit protocol. The optical density value OD at 490nm was measured as shown in Table 1. The OD value results show that each monoclonal phage has good binding property with the specific antibody.
TABLE 1 sample optical Density values
| Numbering | Optical density value | Numbering | Optical density value | Numbering | Optical density value | Numbering | Optical density value |
| 1 | 0.436 | 4 | 0.255 | 7 | 0.280 | 10 | 0.709 |
| 2 | 0.312 | 5 | 0.304 | 8 | 0.299 | ||
| 3 | 0.246 | 6 | 0.357 | 9 | 0.382 |
The method comprises the steps of extracting phage DNA by using an iodide buffer solution method, sending the phage DNA to Beijing Hua Dagen Co Ltd for automatic sequencing by a dye-labelled dideoxy method, and sequencing to obtain 10 different base sequences. As shown in table 2.
Table 210 specific base sequences and corresponding amino acid sequences
The similarity of mimic peptide DNA is detected by applying a nucleic acid Blast system, the amino acid sequences of the 10 screened TGF-beta 1 short peptides are compared with the TGF-beta 1 amino acid sequence shown in SEQ ID NO.21 one by one, 7 relatively concentrated amino acid sequence fragments are found together, and the 7 amino acid sequences are selected to synthesize 7 TGF-beta 1 active polypeptides (Table 3).
MAGAWLRWGLLLWAGLLASSAHGRLRRITYVVHPGPGLAAGALPLSGPPRSRTFNVALNARYSRSSAAAGAPSRASPGVPSERTRRTSKPGGAALQGLRPPPPPPPEPARPAVPGGQLHPNPGGHPAAAPFTKQGRQVVRSKVPQETQSGGGSRLQVHQKQQLQGVNVCGGRCCHGWSKAPGSQRCTKPSCVPPCQNGGMCLRPQLCVCKPGTKGKACETIAAQDTSSPVFGGQSPGAASSWGPPEQAAKHTSSKKADTLPRVSPVAQMTLTLKPKPSVGLPQQIHSQVTPLSSQSVVIHHGQTQEYVLKPKYFPAQKGISGEQSTEGSFPLRYVQDQVAAPFQLSNHTGRIKVVFTPSICKVTCTKGSCQNSCEKGNTTTLISENGHAADTLTATNFRVVICHLPCMNGGQCSSRDKCQCPPNFTGKLCQIPVHGASVPKLYQHSQQPGKALGTHVIHSTHTLPLTVTSQQGVKVKFPPNIVNIHVKHPPEASVQIHQVSRIDGPTGQKTKEAQPGQSQVSYQGLPVQKTQTIHSTYSHQQVIPHVYPVAAKTQLGRCFQETIGSQCGKALPGLSKQEDCCGTVGTSWGFNKCQKCPKKPSYHGYNQMMECLPGYKRVNNTFCQDINECQLQGVCPNGECLNTMGSYRCTCKIGFGPDPTFSSCVPDPPVISEEKGPCYRLVSSGRQCMHPLSVHLTKQLCCCSVGKAWGPHCEKCPLPGTAAFKEICPGGMGYTVSGVHRRRPIHHHVGKGPVFVKPKNTQPVAKSTHPPPLPAKEEPVEALTFSREHGPGVAEPEVATAPPEKEIPSLDQEKTKLEPGQPQLSPGISTIHLHPQFPGIVIEKTSPPVPVEVAPEASTSSASQVIAPTQVTEINECTVNPDICGAGHCINLPVRYTCICYEGYRFSEQQRKCVDIDECTQVQHLCSQGRCENTEGSFLCICPAGFMASEEGTNCIDVDECLRPDVCGEGHCVNTVGAFRCEYCDSGYRMTQRGRCEDIDECLNPSTCPDEQCVNSPGSYQCVPCTEGFRGWNGQCLDVDECLEPNVCANGDCSNLEGSYMCSCHKGYTRTPDHKHCRDIDECQQGNLCVNGQCKNTEGSFRCTCGQGYQLSAAKDQCEDIDECQHRHLCAHGQCRNTEGSFQCVCDQGYRASGLGDHCEDINECLEDKSVCQRGDCINTAGSYDCTCPDGFQLDDNKTCQDINECEHPGLCGPQGECLNTEGSFHCVCQQGFSISADGRTCEDIDECVNNTVCDSHGFCDNTAGSFRCLCYQGFQAPQDGQGCVDVNECELLSGVCGEAFCENVEGSFLCVCADENQEYSPMTGQCRSRTSTDLDVDVDQPKEEKKECYYNLNDASLCDNVLAPNVTKQECCCTSGAGWGDNCEIFPCPVLGTAEFTEMCPKGKGFVPAGESSSEAGGENYKDADECLLFGQEICKNGFCLNTRPGYECYCKQGTYYDPVKLQCFDMDECQDPSSCIDGQCVNTEGSYNCFCTHPMVLDASEKRCIRPAESNEQIEETDVYQDLCWEHLSDEYVCSRPLVGKQTTYTECCCLYGEAWGMQCALCPLKDSDDYAQLCNIPVTGRRQPYGRDALVDFSEQYTPEADPYFIQDRFLNSFEELQAEECGILNGCENGRCVRVQEGYTCDCFDGYHLDTAKMTCVDVNECDELNNRMSLCKNAKCINTDGSYKCLCLPGYVPSDKPNYCTPLNTALNLEKDSDLE(SEQ ID NO.21)。
TABLE 3 sequence selection and design of TGF-beta 1 active Polypeptides
| Sample numbering | Amino acid sequence synthesis |
| 1 | HGRLRRITYVVHPGPGLAAGALPLSGP(SEQ ID NO.22) |
| 2 | HQKQQLQGVNVCGGRCCHGWSKAPGSQRCT(SEQ ID NO.23) |
| 3 | HTSSKKADTLPRVSPVAQMTLTLKPKPSVGL(SEQ ID NO.24) |
| 4 | HSQVTPLSSQSVVIHHGQTQEYVLKPKYFP(SEQ ID NO.25) |
| 5 | HGASVPKLYQHSQQPGKALGTH(SEQ ID NO.26) |
| 6 | HLSDEYVCSRPLVGKQTTYTECCCLYGEAWGM(SEQ ID NO.27) |
| 7 | HLDTAKMTCVDVNECDELNNRMSLCKNAKCINT(SEQ ID NO.28) |
Example 2: synthesis of TGF-beta 1 active polypeptides
7 TGF-beta 1 polypeptide sequences obtained by screening in the embodiment 1 are sent to Wuhanming Hao biotechnology limited to synthesize TGF-beta 1 active polypeptides, the purity is purified to 98%, then disulfide bonds are adopted to form loop at an indefinite point to stabilize a peptide chain structure, and meanwhile, the C end of the polypeptide is amidated and sealed to enhance the stability of the active polypeptides; carrying out rhodamine laser dye labeling on the N end of the polypeptide, and detecting whether the polypeptide can be combined with the fibroblast by identifying the affinity of the active polypeptide with the fibroblast. Making into lyophilized powder, and storing at-20 deg.C.
Example 3: in vitro and in vivo experiments of TGF-beta 1 active polypeptide
Each TGF-. beta.1 active polypeptide of example 2 was used to intervene in cultured fibroblasts, and because TGF-. beta.1 active polypeptides were labeled with rhodamine laser dye, immunofluorescence assays were used to detect their affinity for fibroblasts. The result shows that only the TGF-beta 1 active polypeptide shown in SEQ ID NO.23 can be combined with a specific receptor on a fibroblast.
Further co-culturing TGF-beta 1 active polypeptide shown as SEQ ID NO.23 and human fibroblast, performing in vitro experiment, and setting blank control group, TGF-beta 1 active polypeptide group and TGF-beta 1 growth factor group. By adopting the CCK-8 method, the result shows that compared with a negative control group, the TGF-beta 1 active polypeptide group can promote cell proliferation, has obvious difference (P <0.05) and is dose-dependent, and is shown in the table 3.
TABLE 3 CCK-8 test for the Effect of TGF-. beta.1 active Polypeptides on the proliferation of fibroblasts
TGF-beta 1 active polypeptides as shown in SEQ ID No.23 were further used in vivo experiments: a diabetic rat model is prepared by applying streptozotocin, a round wound surface with the diameter of 2cm is prepared on the back of a rat, the wound surface is periodically subjected to grouping intervention, and different groups of intervention are respectively a TGF-beta 1 active polypeptide gel group, a TGF-beta 1 growth factor group and a blank control group. And (4) taking a picture 14d after the wound, recording the non-healing area of the wound, and calculating the healing rate of the wound. Histopathology and PCR detection are carried out on wound tissues, and the results show that the wound healing rate of the TGF-beta 1 active polypeptide gel group is 85.6%, the wound healing rate of the TGF-beta 1 growth factor group is 83.86%, and the wound healing rate of the blank control group is 60%. Compared with a blank control group, the TGF-beta 1 active polypeptide gel group can obviously promote wound healing (p is less than 0.05).
Therefore, the transforming growth factor beta1 active polypeptide can be used for preparing medicines for treating wound healing, can promote wound healing, effectively reduce inflammation, improve healing efficiency and effect, and has no toxic or side effect on human bodies.
The medicine for treating wound healing comprises an effective amount of transforming growth factor beta1 active polypeptide and pharmaceutically acceptable auxiliary materials.
The medicament for treating wound healing is in any one of an external semisolid preparation, an external solid preparation and an external liquid preparation.
The external semisolid preparation is a paste.
The ointment is gel or emulsion.
The gel consists of transforming growth factor beta1 active polypeptide and a matrix, wherein the dosage of the transforming growth factor beta1 active polypeptide is 2000 IU/g gel matrix-10000 IU/g gel matrix. The dosage of the transforming growth factor beta1 active polypeptide is 8000 IU/g gel substrate.
The gel matrix comprises a mixture of poloxamer 407, carbomer, methylparaben, and heparin.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Sequence listing
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<120> transforming growth factor beta1 active polypeptide and application thereof
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Val Pro Gly Gly Gln Leu His Pro Asn Pro Gly Gly His Pro Ala Ala
115 120 125
Ala Pro Phe Thr Lys Gln Gly Arg Gln Val Val Arg Ser Lys Val Pro
130 135 140
Gln Glu Thr Gln Ser Gly Gly Gly Ser Arg Leu Gln Val His Gln Lys
145 150 155 160
Gln Gln Leu Gln Gly Val Asn Val Cys Gly Gly Arg Cys Cys His Gly
165 170 175
Trp Ser Lys Ala Pro Gly Ser Gln Arg Cys Thr Lys Pro Ser Cys Val
180 185 190
Pro Pro Cys Gln Asn Gly Gly Met Cys Leu Arg Pro Gln Leu Cys Val
195 200 205
Cys Lys Pro Gly Thr Lys Gly Lys Ala Cys Glu Thr Ile Ala Ala Gln
210 215 220
Asp Thr Ser Ser Pro Val Phe Gly Gly Gln Ser Pro Gly Ala Ala Ser
225 230 235 240
Ser Trp Gly Pro Pro Glu Gln Ala Ala Lys His Thr Ser Ser Lys Lys
245 250 255
Ala Asp Thr Leu Pro Arg Val Ser Pro Val Ala Gln Met Thr Leu Thr
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Leu Lys Pro Lys Pro Ser Val Gly Leu Pro Gln Gln Ile His Ser Gln
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Val Thr Pro Leu Ser Ser Gln Ser Val Val Ile His His Gly Gln Thr
290 295 300
Gln Glu Tyr Val Leu Lys Pro Lys Tyr Phe Pro Ala Gln Lys Gly Ile
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Ser Gly Glu Gln Ser Thr Glu Gly Ser Phe Pro Leu Arg Tyr Val Gln
325 330 335
Asp Gln Val Ala Ala Pro Phe Gln Leu Ser Asn His Thr Gly Arg Ile
340 345 350
Lys Val Val Phe Thr Pro Ser Ile Cys Lys Val Thr Cys Thr Lys Gly
355 360 365
Ser Cys Gln Asn Ser Cys Glu Lys Gly Asn Thr Thr Thr Leu Ile Ser
370 375 380
Glu Asn Gly His Ala Ala Asp Thr Leu Thr Ala Thr Asn Phe Arg Val
385 390 395 400
Val Ile Cys His Leu Pro Cys Met Asn Gly Gly Gln Cys Ser Ser Arg
405 410 415
Asp Lys Cys Gln Cys Pro Pro Asn Phe Thr Gly Lys Leu Cys Gln Ile
420 425 430
Pro Val His Gly Ala Ser Val Pro Lys Leu Tyr Gln His Ser Gln Gln
435 440 445
Pro Gly Lys Ala Leu Gly Thr His Val Ile His Ser Thr His Thr Leu
450 455 460
Pro Leu Thr Val Thr Ser Gln Gln Gly Val Lys Val Lys Phe Pro Pro
465 470 475 480
Asn Ile Val Asn Ile His Val Lys His Pro Pro Glu Ala Ser Val Gln
485 490 495
Ile His Gln Val Ser Arg Ile Asp Gly Pro Thr Gly Gln Lys Thr Lys
500 505 510
Glu Ala Gln Pro Gly Gln Ser Gln Val Ser Tyr Gln Gly Leu Pro Val
515 520 525
Gln Lys Thr Gln Thr Ile His Ser Thr Tyr Ser His Gln Gln Val Ile
530 535 540
Pro His Val Tyr Pro Val Ala Ala Lys Thr Gln Leu Gly Arg Cys Phe
545 550 555 560
Gln Glu Thr Ile Gly Ser Gln Cys Gly Lys Ala Leu Pro Gly Leu Ser
565 570 575
Lys Gln Glu Asp Cys Cys Gly Thr Val Gly Thr Ser Trp Gly Phe Asn
580 585 590
Lys Cys Gln Lys Cys Pro Lys Lys Pro Ser Tyr His Gly Tyr Asn Gln
595 600 605
Met Met Glu Cys Leu Pro Gly Tyr Lys Arg Val Asn Asn Thr Phe Cys
610 615 620
Gln Asp Ile Asn Glu Cys Gln Leu Gln Gly Val Cys Pro Asn Gly Glu
625 630 635 640
Cys Leu Asn Thr Met Gly Ser Tyr Arg Cys Thr Cys Lys Ile Gly Phe
645 650 655
Gly Pro Asp Pro Thr Phe Ser Ser Cys Val Pro Asp Pro Pro Val Ile
660 665 670
Ser Glu Glu Lys Gly Pro Cys Tyr Arg Leu Val Ser Ser Gly Arg Gln
675 680 685
Cys Met His Pro Leu Ser Val His Leu Thr Lys Gln Leu Cys Cys Cys
690 695 700
Ser Val Gly Lys Ala Trp Gly Pro His Cys Glu Lys Cys Pro Leu Pro
705 710 715 720
Gly Thr Ala Ala Phe Lys Glu Ile Cys Pro Gly Gly Met Gly Tyr Thr
725 730 735
Val Ser Gly Val His Arg Arg Arg Pro Ile His His His Val Gly Lys
740 745 750
Gly Pro Val Phe Val Lys Pro Lys Asn Thr Gln Pro Val Ala Lys Ser
755 760 765
Thr His Pro Pro Pro Leu Pro Ala Lys Glu Glu Pro Val Glu Ala Leu
770 775 780
Thr Phe Ser Arg Glu His Gly Pro Gly Val Ala Glu Pro Glu Val Ala
785 790 795 800
Thr Ala Pro Pro Glu Lys Glu Ile Pro Ser Leu Asp Gln Glu Lys Thr
805 810 815
Lys Leu Glu Pro Gly Gln Pro Gln Leu Ser Pro Gly Ile Ser Thr Ile
820 825 830
His Leu His Pro Gln Phe Pro Gly Ile Val Ile Glu Lys Thr Ser Pro
835 840 845
Pro Val Pro Val Glu Val Ala Pro Glu Ala Ser Thr Ser Ser Ala Ser
850 855 860
Gln Val Ile Ala Pro Thr Gln Val Thr Glu Ile Asn Glu Cys Thr Val
865 870 875 880
Asn Pro Asp Ile Cys Gly Ala Gly His Cys Ile Asn Leu Pro Val Arg
885 890 895
Tyr Thr Cys Ile Cys Tyr Glu Gly Tyr Arg Phe Ser Glu Gln Gln Arg
900 905 910
Lys Cys Val Asp Ile Asp Glu Cys Thr Gln Val Gln His Leu Cys Ser
915 920 925
Gln Gly Arg Cys Glu Asn Thr Glu Gly Ser Phe Leu Cys Ile Cys Pro
930 935 940
Ala Gly Phe Met Ala Ser Glu Glu Gly Thr Asn Cys Ile Asp Val Asp
945 950 955 960
Glu Cys Leu Arg Pro Asp Val Cys Gly Glu Gly His Cys Val Asn Thr
965 970 975
Val Gly Ala Phe Arg Cys Glu Tyr Cys Asp Ser Gly Tyr Arg Met Thr
980 985 990
Gln Arg Gly Arg Cys Glu Asp Ile Asp Glu Cys Leu Asn Pro Ser Thr
995 1000 1005
Cys Pro Asp Glu Gln Cys Val Asn Ser Pro Gly Ser Tyr Gln Cys Val
1010 1015 1020
Pro Cys Thr Glu Gly Phe Arg Gly Trp Asn Gly Gln Cys Leu Asp Val
1025 1030 1035 1040
Asp Glu Cys Leu Glu Pro Asn Val Cys Ala Asn Gly Asp Cys Ser Asn
1045 1050 1055
Leu Glu Gly Ser Tyr Met Cys Ser Cys His Lys Gly Tyr Thr Arg Thr
1060 1065 1070
Pro Asp His Lys His Cys Arg Asp Ile Asp Glu Cys Gln Gln Gly Asn
1075 1080 1085
Leu Cys Val Asn Gly Gln Cys Lys Asn Thr Glu Gly Ser Phe Arg Cys
1090 1095 1100
Thr Cys Gly Gln Gly Tyr Gln Leu Ser Ala Ala Lys Asp Gln Cys Glu
1105 1110 1115 1120
Asp Ile Asp Glu Cys Gln His Arg His Leu Cys Ala His Gly Gln Cys
1125 1130 1135
Arg Asn Thr Glu Gly Ser Phe Gln Cys Val Cys Asp Gln Gly Tyr Arg
1140 1145 1150
Ala Ser Gly Leu Gly Asp His Cys Glu Asp Ile Asn Glu Cys Leu Glu
1155 1160 1165
Asp Lys Ser Val Cys Gln Arg Gly Asp Cys Ile Asn Thr Ala Gly Ser
1170 1175 1180
Tyr Asp Cys Thr Cys Pro Asp Gly Phe Gln Leu Asp Asp Asn Lys Thr
1185 1190 1195 1200
Cys Gln Asp Ile Asn Glu Cys Glu His Pro Gly Leu Cys Gly Pro Gln
1205 1210 1215
Gly Glu Cys Leu Asn Thr Glu Gly Ser Phe His Cys Val Cys Gln Gln
1220 1225 1230
Gly Phe Ser Ile Ser Ala Asp Gly Arg Thr Cys Glu Asp Ile Asp Glu
1235 1240 1245
Cys Val Asn Asn Thr Val Cys Asp Ser His Gly Phe Cys Asp Asn Thr
1250 1255 1260
Ala Gly Ser Phe Arg Cys Leu Cys Tyr Gln Gly Phe Gln Ala Pro Gln
1265 1270 1275 1280
Asp Gly Gln Gly Cys Val Asp Val Asn Glu Cys Glu Leu Leu Ser Gly
1285 1290 1295
Val Cys Gly Glu Ala Phe Cys Glu Asn Val Glu Gly Ser Phe Leu Cys
1300 1305 1310
Val Cys Ala Asp Glu Asn Gln Glu Tyr Ser Pro Met Thr Gly Gln Cys
1315 1320 1325
Arg Ser Arg Thr Ser Thr Asp Leu Asp Val Asp Val Asp Gln Pro Lys
1330 1335 1340
Glu Glu Lys Lys Glu Cys Tyr Tyr Asn Leu Asn Asp Ala Ser Leu Cys
1345 1350 1355 1360
Asp Asn Val Leu Ala Pro Asn Val Thr Lys Gln Glu Cys Cys Cys Thr
1365 1370 1375
Ser Gly Ala Gly Trp Gly Asp Asn Cys Glu Ile Phe Pro Cys Pro Val
1380 1385 1390
Leu Gly Thr Ala Glu Phe Thr Glu Met Cys Pro Lys Gly Lys Gly Phe
1395 1400 1405
Val Pro Ala Gly Glu Ser Ser Ser Glu Ala Gly Gly Glu Asn Tyr Lys
1410 1415 1420
Asp Ala Asp Glu Cys Leu Leu Phe Gly Gln Glu Ile Cys Lys Asn Gly
1425 1430 1435 1440
Phe Cys Leu Asn Thr Arg Pro Gly Tyr Glu Cys Tyr Cys Lys Gln Gly
1445 1450 1455
Thr Tyr Tyr Asp Pro Val Lys Leu Gln Cys Phe Asp Met Asp Glu Cys
1460 1465 1470
Gln Asp Pro Ser Ser Cys Ile Asp Gly Gln Cys Val Asn Thr Glu Gly
1475 1480 1485
Ser Tyr Asn Cys Phe Cys Thr His Pro Met Val Leu Asp Ala Ser Glu
1490 1495 1500
Lys Arg Cys Ile Arg Pro Ala Glu Ser Asn Glu Gln Ile Glu Glu Thr
1505 1510 1515 1520
Asp Val Tyr Gln Asp Leu Cys Trp Glu His Leu Ser Asp Glu Tyr Val
1525 1530 1535
Cys Ser Arg Pro Leu Val Gly Lys Gln Thr Thr Tyr Thr Glu Cys Cys
1540 1545 1550
Cys Leu Tyr Gly Glu Ala Trp Gly Met Gln Cys Ala Leu Cys Pro Leu
1555 1560 1565
Lys Asp Ser Asp Asp Tyr Ala Gln Leu Cys Asn Ile Pro Val Thr Gly
1570 1575 1580
Arg Arg Gln Pro Tyr Gly Arg Asp Ala Leu Val Asp Phe Ser Glu Gln
1585 1590 1595 1600
Tyr Thr Pro Glu Ala Asp Pro Tyr Phe Ile Gln Asp Arg Phe Leu Asn
1605 1610 1615
Ser Phe Glu Glu Leu Gln Ala Glu Glu Cys Gly Ile Leu Asn Gly Cys
1620 1625 1630
Glu Asn Gly Arg Cys Val Arg Val Gln Glu Gly Tyr Thr Cys Asp Cys
1635 1640 1645
Phe Asp Gly Tyr His Leu Asp Thr Ala Lys Met Thr Cys Val Asp Val
1650 1655 1660
Asn Glu Cys Asp Glu Leu Asn Asn Arg Met Ser Leu Cys Lys Asn Ala
1665 1670 1675 1680
Lys Cys Ile Asn Thr Asp Gly Ser Tyr Lys Cys Leu Cys Leu Pro Gly
1685 1690 1695
Tyr Val Pro Ser Asp Lys Pro Asn Tyr Cys Thr Pro Leu Asn Thr Ala
1700 1705 1710
Leu Asn Leu Glu Lys Asp Ser Asp Leu Glu
1715 1720
<210> 22
<211> 27
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 22
His Gly Arg Leu Arg Arg Ile Thr Tyr Val Val His Pro Gly Pro Gly
1 5 10 15
Leu Ala Ala Gly Ala Leu Pro Leu Ser Gly Pro
20 25
<210> 23
<211> 30
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 23
His Gln Lys Gln Gln Leu Gln Gly Val Asn Val Cys Gly Gly Arg Cys
1 5 10 15
Cys His Gly Trp Ser Lys Ala Pro Gly Ser Gln Arg Cys Thr
20 25 30
<210> 24
<211> 31
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 24
His Thr Ser Ser Lys Lys Ala Asp Thr Leu Pro Arg Val Ser Pro Val
1 5 10 15
Ala Gln Met Thr Leu Thr Leu Lys Pro Lys Pro Ser Val Gly Leu
20 25 30
<210> 25
<211> 30
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 25
His Ser Gln Val Thr Pro Leu Ser Ser Gln Ser Val Val Ile His His
1 5 10 15
Gly Gln Thr Gln Glu Tyr Val Leu Lys Pro Lys Tyr Phe Pro
20 25 30
<210> 26
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 26
His Gly Ala Ser Val Pro Lys Leu Tyr Gln His Ser Gln Gln Pro Gly
1 5 10 15
Lys Ala Leu Gly Thr His
20
<210> 27
<211> 32
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 27
His Leu Ser Asp Glu Tyr Val Cys Ser Arg Pro Leu Val Gly Lys Gln
1 5 10 15
Thr Thr Tyr Thr Glu Cys Cys Cys Leu Tyr Gly Glu Ala Trp Gly Met
20 25 30
<210> 28
<211> 33
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 28
His Leu Asp Thr Ala Lys Met Thr Cys Val Asp Val Asn Glu Cys Asp
1 5 10 15
Glu Leu Asn Asn Arg Met Ser Leu Cys Lys Asn Ala Lys Cys Ile Asn
20 25 30
Thr
Claims (9)
1. A transforming growth factor beta1 active polypeptide is characterized in that the amino acid sequence is shown as SEQ ID NO. 23.
2. Use of a transforming growth factor beta1 active polypeptide according to claim 1 in the manufacture of a medicament for the treatment of wound healing.
3. The use of claim 2, wherein the medicament for the treatment of wound healing comprises an effective amount of a polypeptide active as transforming growth factor beta1 and a pharmaceutically acceptable excipient.
4. The use according to claim 3, wherein the medicament for treating wound healing is in the form of any one of a semi-solid preparation for external use, a solid preparation for external use and a liquid preparation for external use.
5. The use according to claim 4, wherein the semi-solid formulation for external use is a paste.
6. Use according to claim 5, wherein the cream is a gel or an emulsion.
7. The use of claim 6, wherein the gel is comprised of an TGF β 1 active polypeptide and a matrix, wherein the dose of the TGF β 1 active polypeptide is from 2000 IU/g gel matrix to 10000 IU/g gel matrix.
8. The use according to claim 7, wherein the dose of the TGF β 1 active polypeptide is 8000IU per gram of gel matrix.
9. The use of claim 7, wherein the gel base comprises a mixture of poloxamer 407, carbomer, methylparaben, and heparin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210031213.5A CN114409761A (en) | 2022-01-12 | 2022-01-12 | Transforming growth factor beta1 active polypeptide and application thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210031213.5A CN114409761A (en) | 2022-01-12 | 2022-01-12 | Transforming growth factor beta1 active polypeptide and application thereof |
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| Publication Number | Publication Date |
|---|---|
| CN114409761A true CN114409761A (en) | 2022-04-29 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210031213.5A Pending CN114409761A (en) | 2022-01-12 | 2022-01-12 | Transforming growth factor beta1 active polypeptide and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114409761A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113039199A (en) * | 2018-11-15 | 2021-06-25 | 生物科技联合中心 | Activin/bone morphogenic protein 7 chimera: super-active SAB704 and SAB715 and NAB704, NAB715 and NAB204 as noggin-sensitized variants thereof |
-
2022
- 2022-01-12 CN CN202210031213.5A patent/CN114409761A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113039199A (en) * | 2018-11-15 | 2021-06-25 | 生物科技联合中心 | Activin/bone morphogenic protein 7 chimera: super-active SAB704 and SAB715 and NAB704, NAB715 and NAB204 as noggin-sensitized variants thereof |
Non-Patent Citations (2)
| Title |
|---|
| 刘振中等: "转化生长因子-β1噬菌体模拟肽促进成纤维细胞增殖的效果", 山东大学学报（医学版）, vol. 53, no. 3, pages 50 * |
| 宗宪磊等: "转化生长因子β1的关键序列筛选及鉴定", 组织工程与重建外科杂志, vol. 12, no. 3, pages 157 - 158 * |
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