CN108752433B - Antimicrobial peptide CRAMP and application of cyclic peptide thereof in preparation of drugs for removing bacterial biofilms - Google Patents
Antimicrobial peptide CRAMP and application of cyclic peptide thereof in preparation of drugs for removing bacterial biofilms Download PDFInfo
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- CN108752433B CN108752433B CN201810701474.7A CN201810701474A CN108752433B CN 108752433 B CN108752433 B CN 108752433B CN 201810701474 A CN201810701474 A CN 201810701474A CN 108752433 B CN108752433 B CN 108752433B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
The invention relates to an application of antimicrobial peptide CRAMP and cyclic peptide thereof in preparing a medicament for removing a bacterial biofilm, wherein the amino acid sequence of the antimicrobial peptide CRAMP is shown as SEQ ID NO.1, and the head and the tail of the antimicrobial peptide CRAMP are cyclized to obtain the cyclic peptide CRAMP.
Description
Technical Field
The invention belongs to the field of biological medicines, and particularly relates to an antimicrobial peptide CRAMP and a cyclic peptide, and application of the antimicrobial peptide CRAMP and the cyclic peptide in preparation of a medicine for removing a bacterial biofilm.
Background
Bacterial Biofilm (BF) is an organized bacterial mass formed by multiple bacteria adhering to an abiotic or biotic surface, secreting Extracellular Polymeric Substances (EPS), and wrapping themselves therein, and comprises polysaccharides, proteins, extracellular DNA, lipids, and the like, and is an ecosystem with a three-dimensional spatial structure. The bacteria in the form of the biological membrane are protected by EPS, attack of an immune system of an organism and killing of antibacterial drugs can be avoided, drug resistance is enhanced, and meanwhile, the biological membrane can also continuously release the bacteria, so that infection is recurrent and incurable for a long time. It has been reported that biofilm-forming bacteria can exhibit up to 1000 times greater antibiotic resistance than planktonic bacteria, making biofilms clinically more susceptible to intractable chronic infections, severely threatening human and animal health. Therefore, there is an urgent need to find a bioactive substance that acts on bacterial biofilms, especially on mature biofilms.
Disclosure of Invention
In view of the above, an object of the present invention is to provide the use of the antimicrobial peptide CRAMP in the preparation of a medicament for removing bacterial biofilm; the invention also aims to provide the application of the antimicrobial peptide CRAMP in preparing the medicine for treating cystic fibrosis pneumonia; the invention also aims to provide the application of the antimicrobial cyclic peptide CRAMP in the preparation of medicines for clearing bacterial biofilms; the fourth purpose of the invention is to provide the application of the antimicrobial cyclic peptide CRAMP in preparing the medicine for treating cystic fibrosis pneumonia.
In order to achieve the above purpose, the invention provides the following technical scheme:
1. an application of antimicrobial peptide CRAMP in preparing a medicine for removing bacterial biofilm, wherein the amino acid sequence of the antimicrobial peptide CRAMP is shown as SEQ ID NO. 1.
Preferably, the bacterium is pseudomonas aeruginosa.
2. The application of antimicrobial peptide CRAMP to the preparation of drugs for treating cystic fibrosis pneumonia, wherein the amino acid sequence of the antimicrobial peptide CRAMP is shown as SEQ ID NO. 1.
3. The application of the antimicrobial cyclic peptide CRAMP to the preparation of medicines for removing bacterial biofilms, wherein the amino acid sequence of the antimicrobial cyclic peptide CRAMP is shown as SEQ ID NO. 2.
Preferably, the bacterium is pseudomonas aeruginosa.
More preferably, the effective dosage concentration of the antimicrobial cyclic peptide CRAMP is greater than 5 μ M.
4. The application of antimicrobial cyclic peptide CRAMP to the preparation of a medicament for treating cystic fibrosis pneumonia, wherein the amino acid sequence of the antimicrobial cyclic peptide CRAMP is shown as SEQ ID NO. 2.
The invention has the beneficial effects that: the invention synthesizes antimicrobial peptide CRAMP and cyclic peptide, and finds that the antimicrobial peptide CRAMP and cyclic peptide have obvious clearing effect and inhibition formation on mature biomembranes of pseudomonas aeruginosa for the first time, and are obviously superior to control LL-37. Since the fundamental reason for Cystic Fibrosis (CF) pneumonia with high fatality rate in medical clinic is that the mature biomembrane of the pseudomonas aeruginosa is difficult to remove, the research has very important scientific significance and medical clinical value for the treatment of the Cystic fibrosis pneumonia and the deep research of the elimination strategy and mechanism of the biomembrane of the pseudomonas aeruginosa.
Drawings
In order to make the object, technical scheme and beneficial effect of the invention more clear, the invention provides the following drawings for explanation:
FIG. 1 shows the results of CRAMP and LL-37 viable cell count and biofilm amount (A: LL-37; B: CRAMP; broken line: viable cell count of biofilm; histogram: biofilm amount).
FIG. 2 shows the effect of the cyclic peptide CRAMP on the removal of biofilm of the wild standard strain PAO1 of Pseudomonas aeruginosa (broken line: viable count of biofilm; histogram: amount of biofilm).
Fig. 3 is a graph of the effect of different proteases on CRAMP anti-e.coli activity (zone diameter,
n ═ 6) (Neutral protease: neutral protease, Pepsase: pepsin, Trypsase: trypsin).
Detailed Description
Preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings.
Pseudomonas aeruginosa (P.a) is a common pathogenic bacterium for conditioned medium, is a main pathogenic bacterium for chronic lung infection such as Cystic Fibrosis (CF), and is also a common pathogen causing chronic repeated infection of immunocompromised organisms. The bacterium is resistant to various common antibiotics, the infection is easy to relapse and difficult to clear, the main reason is that BF is easy to form, and the bacterium can cause wide infection in animals and plants, is one of the most known bacteria with obvious ecological significance at present. Therefore, the embodiment of the invention takes pseudomonas aeruginosa as an example to research the substance with biological activity on BF.
Example 1 CRAMP antibacterial biofilm study
It is also reported that LL-37 has obvious effect of inhibiting the formation of P.aeruginosa biomembrane in vitro, and meanwhile LL-37 is also observed to have certain effect on the formed mature P.aeruginosa biomembrane, but the inhibiting effect is limited, so that a substance which has more effective bioactivity on the bacterial biomembrane is urgently needed. CRAMP (cathelicidin-Related Antimicrobial peptide) is a biologically active polypeptide present in organs such as testis, spleen, stomach, small intestine and the like of vertebrate mice. Is one of cathelicidins which are one of two main family members of mammal AMPs (mammalian peptides), the structure of the Cathelicidin is mainly alpha-helix, and the amino acid sequence is as follows: GLLRKGGEKIGEKLKKIGQKIKNFFQKLVPQPEQ (SEQ ID NO. 1). However, no report has been made on the effects of CRAMP on bacterial biofilms, particularly on mature biofilms.
Therefore, the results of the biofilm inhibition experiment of p.aeruginosa by selecting CRAMP and LL-37 according to the present invention are shown in fig. 1, in which the number of viable bacteria and the amount of biofilm in the biofilm were observed by a crystal violet staining method and viable bacteria count. The results show that CRAMP has a clear clearing effect on mature biofilms and is significantly superior to the control LL-37.
The method for synthesizing CRAMP in this example is as follows:
the specific synthesis method comprises the following steps:
synthesizing raw materials: the Resin is 2-Chlorotrityl Chloride Resin (Nankai Synthesis technologies, Inc., Tianjin) with a substitution degree of 1.03mmol/g, and the amino acids are Fmoc-Phe-OH (Chengduchinuo, > 99%), Fmoc-Arg (pbf) -OH (Chengduchinuo, > 99%), Fmoc-Ala-OH (Chengduchinuo, > 99%), and the like.
Synthesizing a reagent: DMF (korea of origin), DCM (korea of origin), MEOH (japan of origin), DIEA (nov chemical, 99%), HBTU (haohan biotechnology, 99%).
Deprotection reagents: piperidine (Shanghai chemical company, national drug group, 99%).
Detection reagent: phenol reagent, pyridine reagent, ninhydrin reagent.
And (3) a cracking reagent: 95% cutting fluid: TFA (j.t. baker, 99%), TIS (shanghai deutsche gmbh, 98%), EDT (shanghai deutsche gmbh, 98%), anhydrous ether (shanghai experimenter, 99.7%).
Nitrogen gas: (New gas).
The instrument comprises the following steps: a twelve-channel semi-automatic polypeptide synthesizer (semi-automatic polypeptide synthesizer of Shanghai Qianyao Biotechnology Co., Ltd.); a SHIMADZU high performance liquid chromatograph (model: preparative type, analytical type, software: Class-VP.Sevical System, manufacturer: SHIMADZU); LABCONCO freeze dryer (model: Freezone. plus.6, manufacturer: LABCONCO); centrifuge (Shanghai' an pavilion scientific instrument factory type: TDL-40B)
The polypeptide synthesis steps are as follows: taking the polypeptide 04010029962 as an example, the synthesis sequence is as follows: from the C-terminal to the N-terminal.
(1) Swelling of resin
Placing 2-Chlorotrityl Chloride Resin in a reaction tube, adding DCM (15ml/g), and oscillating for 30 min;
(2) to the first amino acid
Filtering off solvent by sand core, adding 3 times molar excess of Fmoc-Phe-OH amino acid, adding DMF for dissolving, adding 10 times molar excess of DIEA, oscillating for 60min, and blocking with methanol;
(3) deprotection of the amino acid
DMF was removed and 20% piperidine DMF solution (15ml/g) was added for 5min and 20% piperidine DMF solution (15ml/g) was added for 15 min.
(4) Detection of
Pumping out the piperidine solution, taking dozens of resin, washing with ethanol for three times, adding a detection reagent for detection, heating at 105-110 ℃ for 5min, and taking a positive reaction when the resin turns deep blue;
(5) elution is carried out
Eluting twice with DMF (10ml/g), twice with DCM (10ml/g) and twice with DMF (10 ml/g);
(6) condensation of
Protecting amino acid, dissolving with DMF as little as possible, adding into a reaction tube, immediately adding DIEA for tenfold excess, and reacting for 30 min;
(7) detection of
Taking dozens of resin, washing with ethanol for three times, adding a detection reagent for detection, heating at 105-110 ℃ for 5min, and taking colorless as a negative reaction;
(8) elution is carried out
Washed once with DMF (10ml/g), twice with DCM (10ml/g) and twice with DMF (10 ml/g);
(9) repeating the three-six steps, and sequentially connecting the amino acids in the sequence from right to left;
(10) suction-dried, and the resin washed as follows
DMF (10ml/g) twice, methanol (10ml/g) twice, DMF (10ml/g) twice, DCM (10ml/g) twice, and suction-dried for 10 min;
(11) cleavage of polypeptides from resins
Preparing a cutting fluid (10/g), TFA 95%; 1% of water; 2% of EDT; TIS 2%, cutting time: 120 min;
(12) blow-dry washing
Drying the lysate with nitrogen as much as possible, washing with diethyl ether for six times, and then volatilizing at normal temperature;
(13) analyzing and purifying:
purifying the crude product by high performance liquid chromatography;
(14) freeze-drying
Collecting the target polypeptide solution, putting the target polypeptide solution into a freeze dryer for concentration, and freeze-drying the target polypeptide solution into white powder.
Example 2 CRAMP cyclization treatment
Since linear cracps have problems of large side effects and poor stability, this example studies the antibacterial biofilm activity and stability of cyclized cracps.
Firstly, respectively connecting the head and the tail of GLLRKGGEKIGEKLKKIGQKIKNFFQKLVPQPEQ (SEQ ID NO.1) sequence with Cys (cysteine), and obtaining the sequence: CGLLRKGGEKIGEKLKKIGQKIKNFFQKLVPQPEQC (SEQ ID NO.2), cyclizing by a DMSO oxidation method, taking a buffer salt with pH of 8 and 10% DMSO as a cosolvent, and reacting for 10h by magnetic stirring to obtain the cyclic peptide CRAMP, wherein the amino acid sequence of the cyclic peptide CRAMP is shown in SEQ ID NO. 2.
Example 3 validation of the biofilm clearing Effect of the Cyclic peptide CRAMP
The cyclic peptide CRAMP synthesized in example 1 is subjected to anti-P.a biofilm research on a wild standard strain PAO1, and specifically comprises the following steps: in a 96-well cell culture plate, 2 rows are made in parallel each time, mature PAO1 biomembranes are formed in advance for 48h, after PBS liquid is washed, cyclopeptide CRAMP with the concentration of 0 mu M, 0.62 mu M, 1.25 mu M, 2.5 mu M, 5 mu M, 10 mu M and 20 mu M is added for acting for 1h, the quantity of the biomembranes (biofilm mass) is detected by adopting a crystal violet method, the number of viable bacteria of the biomembranes is tested by adopting a TSA plate in the other row, and the independent repetition is carried out for more than 3 times, and the result is shown in figure 2. The results show that the viable count of PAO1 gradually decreases with increasing concentration of cyclic peptide CRAMP (broken line), the amount of biofilm gradually decreases with increasing concentration (histogram) at concentrations above 1.25. mu.M, and the decrease in biofilm amount is evident at concentrations above 5. mu.M. The cyclic peptide CRAMP is shown to have obvious clearing effect on mature biological membranes, and when the concentration is more than 5 mu M, the cyclic peptide CRAMP has obvious clearing effect on PAO1 biological membranes.
Example 4 validation of the stability of the Cyclic peptide CRAMP to the enzyme
The stability test method is that the CRAMP and the cyclic peptide CRAMP are respectively treated by Neutral protease (Neutral protease), pepsin (Pepsase) and trypsin (trypsin) with reaction concentrations of 1mg/mL under the condition of 37 ℃ water bath, and the control is that the CRAMP and the cyclic peptide CRAMP are not treated by enzyme. Coli was observed again, and the results are shown in fig. 3. As a result, it was found that CRAMP is unstable to pepsin and trypsin, and the stability after cyclization treatment is significantly improved. Thus, treatment with cyclized CRAMP not only provides biofilm removal, but also provides significant stability improvements.
Finally, it is noted that the above-mentioned preferred embodiments illustrate rather than limit the invention, and that, although the invention has been described in detail with reference to the above-mentioned preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the scope of the invention as defined by the appended claims.
Sequence listing
<110> university of southwest
<120> antimicrobial peptide CRAMP and application of cyclic peptide thereof in preparation of drugs for removing bacterial biofilms
<160> 2
<170> SIPOSequenceListing 1.0
<210> 1
<211> 34
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 1
Gly Leu Leu Arg Lys Gly Gly Glu Lys Ile Gly Glu Lys Leu Lys Lys
1 5 10 15
Ile Gly Gln Lys Ile Lys Asn Phe Phe Gln Lys Leu Val Pro Gln Pro
20 25 30
Glu Gln
<210> 2
<211> 36
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 2
Cys Gly Leu Leu Arg Lys Gly Gly Glu Lys Ile Gly Glu Lys Leu Lys
1 5 10 15
Lys Ile Gly Gln Lys Ile Lys Asn Phe Phe Gln Lys Leu Val Pro Gln
20 25 30
Pro Glu Gln Cys
35
Claims (4)
1. The application of the antimicrobial peptide CRAMP in the preparation of the medicine for eliminating the bacterial biofilm is characterized in that: the amino acid sequence of the antimicrobial peptide CRAMP is shown as SEQ ID NO. 1; the bacteria are pseudomonas aeruginosa; the effective dosage concentration of the antimicrobial peptide CRAMP is greater than 5 μ M.
2. The application of the antimicrobial peptide CRAMP in the preparation of the medicine for treating cystic fibrosis pneumonia is characterized in that: the amino acid sequence of the antimicrobial peptide CRAMP is shown as SEQ ID NO. 1; the effective dosage concentration of the antimicrobial peptide CRAMP is greater than 5 μ M.
3. The application of the antimicrobial cyclic peptide CRAMP in the preparation of the medicines for clearing bacterial biofilms is characterized in that: the amino acid sequence of the antimicrobial cyclopeptide CRAMP is shown in SEQ ID NO.2, the bacteria are pseudomonas aeruginosa, and the effective dosage concentration of the antimicrobial cyclopeptide CRAMP is more than 5 mu M; the antimicrobial cyclic peptide CRAMP is prepared by cyclizing the antimicrobial peptide CRAMP with an amino acid sequence shown as SEQ ID NO.1 by a DMSO oxidation method, using buffer salt pH =8 and 10% DMSO as a cosolvent, and performing magnetic stirring reaction for 10 h.
4. The application of antimicrobial cyclic peptide CRAMP in preparing a medicine for treating cystic fibrosis pneumonia is characterized in that: the amino acid sequence of the antimicrobial cyclic peptide CRAMP is shown as SEQ ID NO. 2; an effective dosage concentration of the antimicrobial cyclic peptide CRAMP is greater than 5 μ M; the antimicrobial cyclic peptide CRAMP is prepared by cyclizing the antimicrobial peptide CRAMP with an amino acid sequence shown as SEQ ID NO.1 by a DMSO oxidation method, using buffer salt pH =8 and 10% DMSO as a cosolvent, and performing magnetic stirring reaction for 10 h.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104387452A (en) * | 2014-11-25 | 2015-03-04 | 中国人民解放军第三军医大学第一附属医院 | Biological film inhibiting peptide and application thereof |
| CN105566452A (en) * | 2016-01-22 | 2016-05-11 | 北京农学院 | Antibacterial peptide with annular structure and preparation method and application thereof |
| CN107405377A (en) * | 2015-03-12 | 2017-11-28 | 三井化学株式会社 | The destruction methods of excretion body, the separation method for destroying kit and the excretion body from normal cell of excretion body |
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| WO2008140582A2 (en) * | 2006-11-22 | 2008-11-20 | Emory University | Production of anti-microbial peptides |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104387452A (en) * | 2014-11-25 | 2015-03-04 | 中国人民解放军第三军医大学第一附属医院 | Biological film inhibiting peptide and application thereof |
| CN107405377A (en) * | 2015-03-12 | 2017-11-28 | 三井化学株式会社 | The destruction methods of excretion body, the separation method for destroying kit and the excretion body from normal cell of excretion body |
| CN105566452A (en) * | 2016-01-22 | 2016-05-11 | 北京农学院 | Antibacterial peptide with annular structure and preparation method and application thereof |
Non-Patent Citations (5)
| Title |
|---|
| "Derivatives of the Mouse Cathelicidin-Related Antimicrobial Peptide (CRAMP) Inhibit Fungal and Bacterial Biofilm Formation";Katrijn De Brucker 等;《Antimicrob Agents Chemother》;20140630;第58卷(第9期);第5395-5404页 * |
| "Human Host Defense Peptide LL-37 Prevents Bacterial Biofilm Formation";Joerg Overhage 等;《INFECTION AND IMMUNITY》;20080630;第76卷(第9期);第4176-4182页 * |
| "Inhibition and Eradication of Pseudomonas aeruginosa Biofilms by Host Defence Peptides";Hongwei Chen 等;《Sci Rep》;20180711;第8卷;第1-10页 * |
| "抗茵肽在下呼吸道感染茵中的";刘培培 等;《中国医师进修杂志》;20140710;第37卷(第19期);第71-73页 * |
| "抗菌肽抑制细菌生物膜的研究现状";王宏岩 等;《中国微生态学杂志》;20150930;第27卷(第9期);第1100-1104页 * |
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