CN117777244A - Compound and synthetic method and application thereof - Google Patents
Compound and synthetic method and application thereof Download PDFInfo
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- CN117777244A CN117777244A CN202310697907.7A CN202310697907A CN117777244A CN 117777244 A CN117777244 A CN 117777244A CN 202310697907 A CN202310697907 A CN 202310697907A CN 117777244 A CN117777244 A CN 117777244A
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
The invention relates to the technical field of anticancer drug synthesis, and particularly discloses a compound, a synthesis method and application thereof, wherein the compound is subjected to molecular transformation according to the structural characteristics of antibacterial peptide LL-37 to obtain antibacterial peptide LK-24 molecules, and stapling peptide transformation and amino acid replacement are performed again to obtain double stapling peptide StLK-24; after chemical modification, 3' -dA and PTX are respectively connected to the amino terminal and the carboxyl terminal of StLK-24 to obtain the compound. The compound synthesized by the invention has the inhibition rate to SW1990 human pancreatic cancer cells and ME-180 human cervical epidermoid cancer cells, provides a new thought for developing novel anticancer drugs, and can induce the expression of autophagy related proteins LC 3-II and truncated fragments tATG5N and tBucolin-1C.
Description
Technical Field
The invention relates to the technical field of cancer drug synthesis, in particular to a compound and a synthesis method and application thereof.
Background
Cancer is a serious threat to human health, the toxic and side effects of traditional anticancer drugs greatly limit the exertion of the curative effect, and research and development of new anticancer drugs and treatment strategies are particularly urgent, wherein the dosage of the drugs can be greatly reduced by combined administration, the complementary advantage effect is exerted, and the anticancer curative effect is enhanced. Cancer is one of the malignant diseases facing the world, and no effective treatment means exists at present.
Cancer is a serious disease affecting human health, and development of anticancer drugs has been a focus of attention. Many small molecule compounds such as Paclitaxel (PTX), cordycepin (Co) and antimicrobial peptides (Antimicrobial peptide, AMP) have been used in the treatment of cancer, but PTX has some cytotoxicity such as severe anaphylaxis, neurotoxicity, hematologic toxicity, etc. in clinical application, so that the dosage of PTX is limited; the active ingredient of cordycepin,3 '-deoxyadenosine (3' -dA), is easily hydrolyzed rapidly in vivo by adenosine deaminase (Adenosine deaminase, ADA), and only a very small amount of drug is delivered into cancer cells to play a role; natural AMPs also suffer from the disadvantage of unstable properties, being very susceptible to protease hydrolysis and loss of activity, and the affinity of antimicrobial peptides for cancer cells is weaker than bacteria. The above drawbacks greatly limit the clinical application of these small molecular compounds, reflect that the toxic and side effects of many traditional anticancer drugs become an indistinct dilemma that severely influences the important limiting factors of the efficacy of the traditional anticancer drugs, and find new anticancer drugs and therapeutic strategies with low toxicity and high efficiency are becoming urgent. The combined administration is a relatively effective treatment mode at present, can greatly reduce the dosage of medicines, plays a complementary advantage role, enhances the anticancer curative effect, but is limited to simple mixing of a plurality of medicines.
Paclitaxel (PTX) is a common chemotherapeutic drug for treating cancers, but has lower safety and effectiveness, cordycepin (3' -dA) also has certain cancer inhibiting activity, and antibacterial peptides (antimicrobial peptide, AMP) have the same cancer inhibiting activity after being modified into anticancer peptides by molecules, but are easy to be hydrolyzed by protease in cells to lose activity, so that the development of novel anticancer drugs with good stability and strong cancer inhibiting activity is a problem to be solved urgently at present.
Disclosure of Invention
The invention provides a cordycepin-bisstimulin-taxol compound, a synthesis method and application thereof, and the 3' -dA-StLK-24-PTX compound synthesized by the invention has the inhibition rate on SW1990 human pancreatic cancer cells and ME-180 human cervical epidermoid cancer cells, provides a new idea for developing novel anticancer drugs, and can induce the expression of autophagy related proteins LC 3-II and truncated fragments tATG5N and tBuclin-1C.
The first object of the invention is to provide a compound, according to the structural characteristics of antibacterial peptide LL-37, the amino acids of the alpha-helical region, the beta-sheet region, the transmembrane structure, the signal peptide, the charge, the hydrophobic region and the hydrophilic region are subjected to molecular transformation to obtain antibacterial peptide LK-24 molecules with high hydrophobicity, and stapling peptide transformation and amino acid replacement are performed again to obtain double stapling peptide StLK-24;
respectively carrying out chemical modification on 3' -dA and PTX; the modified 3' -dA is connected to the amino end of StLK-24, and the modified PTX is connected to the carboxyl end of StLK-24, so that the compound is obtained.
Further, the synthesis process of the double-staple peptide StLK-24 comprises the following steps: the 13 th to 36 th amino acid of the antibacterial peptide LL-37 is reserved, individual amino acid at the carboxyl end is replaced, the hydrophobicity is improved, the antibacterial peptide LK-24 molecule is obtained, and the modified double-staple peptide StLK-24 is obtained by stapling peptide modification and amino acid replacement of LK-24.
Further, the compound is a cordycepin-bisstaple peptide-taxol compound, abbreviated as 3' -dA-StLK-24-PTX, and has the structural formula:
the second object of the present invention is to provide a synthesis method of the above compound, wherein the synthesis process of the 3' -dA-StLK-24-PTX compound specifically comprises:
s1, modifying antibacterial peptide LL-37 to obtain StLK-24, adding cysteine (Cys, C) at the carboxyl end of StLK-24 to form StLK-24-C, and performing addition reaction between the sulfhydryl of the cysteine and double bond in Mal on PTX-Mal to obtain a StLK-24-PTX compound;
s2, condensing 5' -COOH in the modified 3' -dA structure with the amino terminal of StLK-24 in the StLK-24-PTX compound to form a peptide bond, so as to prepare the 3' -dA-StLK-24-PTX compound.
Further, in S1, the route of obtaining StLK-24-C by molecular modification of the antibacterial peptide LK-24 is as follows:
a third object of the present invention is to provide the use of the above-mentioned compounds for the preparation of a medicament for the treatment of cancer.
Further, the anticancer means anti-cervical cancer and anti-pancreatic cancer.
Further, the cordycepin-bisstaple peptide-taxol compound can be used for preparing an inducer of autophagy-related proteins LC 3-II and truncated fragments tATG5N and tBucolin-1C.
Compared with the prior art, the invention has the beneficial effects that:
1. the invention takes antibacterial peptide, cordycepin (3 '-dA) and taxol as materials, combines bioinformatics technology, carries out multiple molecular reconstruction on antibacterial peptide molecule LL-37 to obtain double-staple peptide StLK-24, carries out chemical modification on cordycepin and taxol, and synthesizes 3' -dA-StLK-24-PTX compound by utilizing organic synthesis technology;
the invention develops a new way to reform the antibacterial peptide molecule into the double-staple peptide StLK-24 with cancer inhibiting activity, then combines with the tumor chemotherapy drug taxol and the cordycepin which is subjected to chemical modification to form the cordycepin-antibacterial peptide-taxol compound, and MTT detects the inhibition rate of the compound on SW1990 human pancreatic cancer cells and ME-180 human cervical epidermoid cancer cells, thereby providing a new thought for developing novel anticancer drugs.
2. According to the invention, PTX and 3'-dA are subjected to structural modification, LK-24 antibacterial peptide is further subjected to stapling modification, a more stable (i, i+4) double-stapling peptide structure (stailed LK-24, stLK-24) is obtained, stLK-24 is taken as a framework, a reaction route is designed by applying an organic synthesis technology, the amino end of StLK-24 is connected with the 3' -dA subjected to structural modification, the carboxyl end is connected with PTX, the 3'-dA-StLK-24-PTX containing three monomer components of cordycepin, taxol and antibacterial peptide is synthesized, and MTT experiments show that the inhibition rate of the compound 3' -dA-StLK-24-PTX with the concentration of 10 mu m on SW1990 and Me180 cancer cell proliferation reaches 99.16% and 99.87%, respectively, which is obviously higher than that of other test groups; western blotting showed that 3' -dA-StLK-24-PTX compound can induce the expression of autophagy related protein LC 3-II and truncated fragment tATG5N and tBucolin-1C, revealing the anti-tumor mechanism of the compound by inducing autophagy of cancer cells and mediating apoptosis of cells by tATG5N and tBucolin-1C. The synthesis of the compound lays a foundation for the screening of novel antitumor drugs.
Drawings
In order to more clearly illustrate the embodiments of the invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, it being obvious that the drawings in the following description are only some embodiments of the invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a technical scheme of the synthesis of 3' -dA-StLK-24-PTX compounds;
in the figure, A represents a modification process of cordycepin (3' -dA);
b represents a modification process for obtaining paclitaxel-Mal after modification of PTX;
c is the process of obtaining StLK-24-C by molecular modification of antibacterial peptide LK-24;
d is a process of obtaining 3'-dA-StLK-24 by using the modified 3' -dA and StLK-24-C reaction;
e is a process of synthesizing 3'-dA-StLK-24 using 3' -dA-StLK-24 and PTX-Mal;
in the figure, a: cordycepin (3' -dA); b: paclitaxel (PTX); c: maleimide propionic acid (Mal); d: paclitaxel-maleimide propionic acid (PTX-Mal); e: antibacterial peptide LK-24; f: the modified double-staple peptide StLK-24; g: cordycepin-di-staple peptide (3' -dA-StLK-24); h: cordycepin-di-staple peptide-paclitaxel (3' -dA-StLK-24-PTX).
FIG. 2 shows the structure of 3' -dA-StLK-24-PTX compound.
FIG. 3 shows the bacteriostatic effect of 3' -dA-StLK-24-PTX compounds on E.coli and S.aureus.
FIG. 4 shows the inhibitory activity of 3' -dA-StLK-24-PTX compounds on SW1990 cancer cells by MTT assay.
FIG. 5 shows the MTT assay for the anticancer activity of 3' -dA-StLK-24-PTX compounds against Me180 cancer cells.
FIG. 6 shows the detection of hemolysis of sheep erythrocytes by the 3' -dA-StLK-24-PTX compound by the enzyme-labeled method.
FIG. 7 shows the western blotting detection of the expression of LC 3-II, tBucolin-1C and tATG5N in SW1990 cancer cells;
in the figure, A is the expression of LC 3-II in SW1990 cancer cells;
b is the expression of tBucolin-1C in SW1990 cancer cells;
c is the expression of tATG5N in SW1990 cancer cells.
FIG. 8 shows the western blotting detection of LC 3-II, tATG5N and tBucolin-1C expression in Me180 cancer cells;
in the figure, A is the expression of LC 3-II in Me180 cancer cells;
b is the expression of tBucolin-1C in Me180 cancer cells;
c is the expression of tATG5N in Me180 cancer cells.
Detailed Description
The following detailed description of specific embodiments of the invention is, but it should be understood that the invention is not limited to specific embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention. The experimental methods described in the examples of the present invention are conventional methods unless otherwise specified, and materials, reagents, etc. used in the examples described below are commercially available.
According to structural characteristics of the antibacterial peptide LL-37, the invention carries out molecular modification on the alpha-helical region, the beta-sheet region, the transmembrane structure, the signal peptide, the charge, the hydrophobic region and the hydrophilic region of the antibacterial peptide LL-37, retains amino acids 13-36, replaces individual amino acids at the carboxyl end, improves hydrophobicity to obtain antibacterial peptide LK-24 molecules composed of 24 amino acids, and finds out that LK-24 has stronger antibacterial activity and low hemolytic property than LL-37 through a bacteriostasis ring experiment, an MTT experiment and a hemolysis experiment, further modifies LK-24 into a double-staple peptide StLK-24, carries out chemical modification on 3'-dA and PTX, modifies 5' -OH of 3'-dA into 5' -COOH, modifies 2'-OH of PTX into a PTX-Mal structure, synthesizes a 3' -dA-StLK-24-PTX compound through an organic synthesis technology, and MTT detects the compound to inhibit ME 0 human pancreatic cancer cells and-180 human cervical epidermoid cancer cells, thereby providing a new development concept for novel anticancer drugs.
Example 1: cordycepin-di-staple peptide-taxol compound and its synthesis process.
1. Modification of 3' -dA, PTX and molecular engineering of antibacterial peptides
1. Modification of 3' -dA
The OTBS is utilized to protect the 2' -hydroxyl in the 3' -dA structure, and the 5' -hydroxyl in the 3' -dA structure is modified into the 5' -carboxyl, so that the peptide bond is conveniently formed by condensation with the amino terminal of StLK-24.
2. Modification of PTX
The 2' -hydroxyl group in the PTX structure is reacted with the carboxyl group in the maleimide propionic acid (Mal) structure to form an ester (PTX-Mal).
3. Molecular engineering of antimicrobial peptides
According to literature reports, antibacterial peptide databases (http:// APs. Un. Edu/AP/main. Php) and bioinformatics analysis, the most representative antibacterial peptide LL-37 molecules are screened, and then according to the characteristics of alpha-helical region, beta-sheet region, transmembrane structure, signal peptide, charge, hydrophobic region, hydrophilic region amino acid and the like of LL-37, LL-37 with the amino acid sequence shown as SEQ ID NO.1 is subjected to molecular modification to obtain antibacterial peptide LK-24 (with the amino acid sequence shown as SEQ ID NO. 2) composed of 24 amino acids, LK-24 is subjected to stapling peptide modification and amino acid replacement again according to the reported design principle of stapling peptide, and then, stLK-24 (shown as Table 1) with the modified amino acid sequence shown as SEQ ID NO.3 is obtained.
TABLE 1StLK-24 design
Note that: x in StLK-24 is the (i+4) double staple position.
2. Synthesis of 3' -dA-StLK-24-PTX compound
1. Synthesis of StLK-24-C-Mal-PTX (StLK-24-PTX) compound
Cysteine (Cys, C) is added at the carboxyl end of StLK-24 to form StLK-24-C, and the addition reaction is carried out between the sulfhydryl of the cysteine and the double bond in Mal on PTX-Mal, so that the StLK-24-C-Mal-PTX (StLK-24-PTX) compound is formed.
2. Synthesis of 3' -dA-StLK-24-PTX compound
Modification of 5' -OH of 3' -dA structural formula to 5' -COOH (modification of 3' -dA), the 5' -COOH in the modified 3' -dA structure was condensed with the amino terminus of StLK-24 in the StLK-24-PTX compound to form a peptide bond, to prepare a 3' -dA-StLK-24-PTX compound. The technical route is shown in figure 1, and the structure of the finally synthesized 3' -dA-StLK-24-PTX compound is shown in figure 2.
3. Synthesis of other Compounds 3'-dA-LK-24 and 3' -dA-StLK-24
1. The molecular structural formula of the 3' -dA-LK-24 is:
the amino acids of the spiral region, the beta-folding region, the transmembrane structure, the signal peptide, the charge, the hydrophobic region and the hydrophilic region of the LL-37 antibacterial peptide are changed by analyzing the secondary structure, the transmembrane region hydrophobicity, the C-terminal amphipathy, the charge offset, the spiral length, the membrane protein topology and the like of the LL-37 to obtain the novel antibacterial peptide LK-24 after molecular modification, and then the 5'-OH of the 3' -dA structural formula is modified into 5'-COOH by utilizing an organic synthesis technology to be condensed with the amino terminal of the LK-24 to form a 3' -dA-LK-24 compound, namely the cordycepin-antibacterial peptide conjugate.
2. 3' -dA-StLK-24: condensing 5' -COOH in the modified 3' -dA structure with the amino terminal of StLK-24 to form a peptide bond, thereby obtaining 3' -dA-StLK-24.
Example 2: application research of cordycepin-bisstaple peptide-taxol compound.
1. Study on antibacterial activity and cancer-inhibiting activity of cordycepin-bisstapling peptide-taxol compound
1. Antibacterial Activity study of 3' -dA-StLK-24-PTX Compounds
Antibacterial effects of anti-3' -dA-LK-24-PTX on E.coli and Staphylococcus aureus were examined using E.coli (ATCC 8739) and Staphylococcus aureus (ATCC 25923) as test strains, respectively.
2. Cancer inhibiting Activity of 3' -dA-StLK-24-PTX Compounds
The logarithmic phase SW1990 and Me180 cancer cells were collected, 30. Mu.L of 1640 (serum-free) medium was sequentially added, 10. Mu.L of Actinomycin D was added, and LK-24, 3'-dA, PTX, 3' -dA-LK-24-PTX were added, respectively, so that the final concentrations were 100. Mu.M, 80. Mu.M, 60. Mu.M, 40. Mu.M, 20. Mu.M, 10. Mu.M, 1. Mu.M, PTX were set to a concentration group of 10. Mu.M, and the cell suspension concentration was adjusted to 1X 10. Mu.M 6 Per mL, adding 96-well plate and 100 μl of each well, repeating each experiment four times, incubating at 37deg.C for 48 hr with 5% CO2, observing cell morphology under inverted microscope, adding 10 μl of WST-1 solution (5 mg/mL, i.e. 0.5% WST-1) per well, and continuously culturing for 4 hr with direct ELISA (enzyme-linked immunosorbent assay) OD 570 The absorbance of each well was measured at nm, and the cancer suppressing effect of LK-24, stLK-24, 3'-dA, PTX, 3' -dA-LK-24, 3'-dA-StLK-24, 3' -dA-LK-24-PTX was evaluated by taking an average value.
3. Hemolytic Activity of 3' -dA-StLK-24-PTX Compounds
Fresh New Zealand white rabbit whole blood was collected, heparin anticoagulated, centrifuged at 3000r/min at 4℃for 10min to obtain a pellet, which was washed with physiological saline and resuspended at 8% (v/v). 100. Mu.L of the red blood cell suspension was mixed with 100. Mu.L of 3' -dA-StLK-24-PTX solutions of different concentrations (5, 10, 20, 50, 100, 200, 300, 400, 500. Mu.L/mL). The mixed system is placed in a 37 ℃ incubator for incubation for 1h, taken out and centrifuged for 10min at 3000r/min at 4 ℃, the supernatant is taken out, and the absorbance at 570nm is measured by using an enzyme-labeled instrument. Positive control group was set: 0.1% TritionX-100 100. Mu.L; negative control group: 15. Mu.L of water was supplemented with physiological saline to 100. Mu.L. The hemolytic activities of LK-24, stLK-24, 3' -dA, PTX, 3' -dA-LK-24, 3' -dA-StLK-24 were studied similarly.
Percent hemolysis was calculated as follows: hemolysis (%) = (test group absorbance-negative control group absorbance)/(positive control group absorbance-negative control group absorbance) ×100%.
4. 3' -dA-StLK-24-PTX compounds induce response of cancer cells to autophagy and apoptosis
SW1990 and Me180 cancer cells were treated with 3' -dA-StLK-24-PTX compounds, respectively, cell pellets were collected every 8 hours, total proteins were extracted, and the LC 3-II, truncated components tATG5N and tBuclin-1C content in the cancer cells were detected by western blotting after protein quantification to evaluate the degree of response of the cancer cells to 3' -dA-StLK-24-PTX compounds and LK-24, stLK-24, 3' -dA, PTX, 3' -dA-LK-24, 3' -dA-StLK-24.
2. Experimental results
1. 3' -dA-StLK-24-PTX compound with broad-spectrum antibacterial activity
The inhibition of the two bacteria by the 3' -dA-LK-24-PTX was examined using E.coli (ATCC 8739) and Staphylococcus aureus (S.aureus, ATCC 25923) as the test bacteria, and a bacteriostasis curve was drawn, which showed that the 3' -dA-StLK-24-PTX compound at a concentration of 0.65. Mu.M could kill more than 90% of E.coli and Staphylococcus aureus, indicating that the 3' -dA-StLK-24-PTX compound had extremely strong bacteriostasis activity (FIG. 3).
2. 3' -dA-StLK-24-PTX compound with strong cancer inhibiting activity and low hemolytic activity
By means of organic synthesis technology, the antibacterial peptide LK-24 modified by SAAP-148 is coupled with taxol (PTX) and 3'-dA for the first time to obtain the 3' -dA-StLK-24-PTX compound.
MTT experiment results show that the inhibition rate of the 3' -dA-StLK-24-PTX compound with the concentration of 10 mu M on SW1990 and Me180 cancer cell proliferation reaches 99.16% and 99.87%, respectively, which is higher than that of other experiment groups (figure 4 and figure 5), and hemolysis experiments show that the hemolysis of the compound with the concentration of 128 mu M on sheep red blood cells is lower than 20% (16.84% and figure 6), so that the compound has extremely strong inhibition effect on cancer cells in vitro.
3. 3' -dA-StLK-24-PTX compound can induce autophagy and apoptosis of cancer cells
After SW1990 and Me180 cancer cells were treated with the compound, the content of LC 3-II, truncated components tATG5N and tBucolin-1C in the cancer cells was examined by western blotting, and it was found that the content of LC 3-II, tATG5N and tBucolin-1C in the cancer cells was increased after the compound treatment, indicating that the compound induced the response of the cancer cells to autophagy and apoptosis (FIG. 7, FIG. 8).
While preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. It is therefore intended that the following claims be interpreted as including the preferred embodiments and all such alterations and modifications as fall within the scope of the invention.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention also include such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.
Claims (8)
1. A compound which is characterized in that according to the structural characteristics of antibacterial peptide LL-37, amino acids of an alpha-helical region, a beta-sheet region, a transmembrane structure, a signal peptide, electric charge, a hydrophobic region and a hydrophilic region are subjected to molecular transformation to obtain antibacterial peptide LK-24 molecules with high hydrophobicity, and stapling peptide transformation and amino acid replacement are performed again to obtain double stapling peptide StLK-24;
respectively carrying out chemical modification on 3' -dA and PTX; the modified 3' -dA is connected to the amino end of StLK-24, and the modified PTX is connected to the carboxyl end of StLK-24, so that the compound is obtained.
2. The compound of claim 1, wherein the double-staple peptide StLK-24 synthesis process is: the 13 th to 36 th amino acid of the antibacterial peptide LL-37 is reserved, individual amino acid at the carboxyl end is replaced, the hydrophobicity is improved, the antibacterial peptide LK-24 molecule is obtained, and the modified double-staple peptide StLK-24 is obtained by stapling peptide modification and amino acid replacement of LK-24.
3. The compound of claim 2, wherein the compound is a cordycepin-di-staple peptide-paclitaxel compound, abbreviated as 3' -dA-StLK-24-PTX, having the structural formula:
4. a method for synthesizing the compound of claim 3, wherein the synthesis process of the 3' -dA-StLK-24-PTX compound specifically comprises the following steps:
s1, modifying antibacterial peptide LL-37 to obtain StLK-24, adding cysteine at the carboxyl end of StLK-24 to form StLK-24-C, and performing addition reaction between the sulfhydryl group of the cysteine and double bond in Mal on PTX-Mal to obtain a StLK-24-PTX compound;
s2, condensing 5' -COOH in the modified 3' -dA structure with the amino terminal of StLK-24 in the StLK-24-PTX compound to form a peptide bond, so as to prepare the 3' -dA-StLK-24-PTX compound.
5. The method for synthesizing a compound according to claim 4, wherein in S1, the antibacterial peptide LK-24 is obtained by molecular modification of StLK-24-C by the route:
6. use of a compound according to any one of claims 1-3 for the preparation of a medicament for the treatment of cancer.
7. The use of a compound according to claim 6 for the preparation of a medicament for the treatment of cancer, wherein the cancer is anti-cervical cancer and anti-pancreatic cancer.
8. The use of a cordycepin-bisstaple peptide-paclitaxel compound according to claim 6 for the preparation of anticancer drugs, wherein the cordycepin-bisstaple peptide-paclitaxel compound can be used for the preparation of inducers of autophagy-related proteins LC 3-ii and truncated fragments ttatg 5N and tBeclin-1C.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107602666A (en) * | 2017-09-30 | 2018-01-19 | 中国人民解放军第二军医大学 | A kind of thioesters stapler peptide and preparation method and application |
| CN112321684A (en) * | 2020-11-03 | 2021-02-05 | 红河学院 | Paclitaxel-antibacterial peptide conjugate, synthesis method and application of paclitaxel-antibacterial peptide conjugate in inhibiting cancer activity |
| CN113651871A (en) * | 2021-08-03 | 2021-11-16 | 东北农业大学 | Anti-enzymolysis alpha-helical antibacterial peptide bound by all-carbon hydrogen side chain, preparation method and application |
| CN114181293A (en) * | 2021-12-06 | 2022-03-15 | 郑州大学 | Humanized antibacterial peptide LL-37 modified body and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107602666A (en) * | 2017-09-30 | 2018-01-19 | 中国人民解放军第二军医大学 | A kind of thioesters stapler peptide and preparation method and application |
| CN112321684A (en) * | 2020-11-03 | 2021-02-05 | 红河学院 | Paclitaxel-antibacterial peptide conjugate, synthesis method and application of paclitaxel-antibacterial peptide conjugate in inhibiting cancer activity |
| CN113651871A (en) * | 2021-08-03 | 2021-11-16 | 东北农业大学 | Anti-enzymolysis alpha-helical antibacterial peptide bound by all-carbon hydrogen side chain, preparation method and application |
| CN114181293A (en) * | 2021-12-06 | 2022-03-15 | 郑州大学 | Humanized antibacterial peptide LL-37 modified body and application thereof |
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