CN106916205A - Antibacterial hexapeptide and its derivative and application - Google Patents
Antibacterial hexapeptide and its derivative and application Download PDFInfo
- Publication number
- CN106916205A CN106916205A CN201710211273.4A CN201710211273A CN106916205A CN 106916205 A CN106916205 A CN 106916205A CN 201710211273 A CN201710211273 A CN 201710211273A CN 106916205 A CN106916205 A CN 106916205A
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- Prior art keywords
- antibacterial
- trp
- arg
- hexapeptide
- antibacterial peptide
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- 241000589291 Acinetobacter Species 0.000 claims abstract description 30
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- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims abstract description 10
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention discloses a kind of antibacterial hexapeptide, sequence is：Arg‑Arg‑Trp‑Trp‑Arg‑Trp.It is applied in the medicine for prepare treatment or prevention bacterium infection.The present invention also provides a kind of antibacterial hexapeptide derivatives, and the sequence of the antibacterial hexapeptide derivatives is：Arg Arg Trp Trp Arg Trp β phenyl ethylamines.It is applied in the medicine for prepare treatment or prevention bacterium infection.The bacterium is resistance Acinetobacter bauamnnii.The antibacterial hexapeptide and its phenyl ethylamine trim of engineer's synthesis that the present invention is provided, it is convenient to obtained using solid-phase synthesis.The synthetic antibacterial peptide and its derivative have wide spectrum killing activity to gram-positive bacteria, Gram-negative bacteria, especially its derivative shows stronger antibacterial activity to resistance Acinetobacter bauamnnii, hemolytic toxicity is minimum, can be applied in the medicine for treat or prevent the disease caused by resistance Acinetobacter bauamnnii.
Description
Technical field
The present invention relates to a kind of antibacterial hexapeptide and its derivative and their application, belong to biological technical field.
Background technology
The annual bacterium infection sufferer in the whole world is up to 1,500,000,000 people, wherein death toll 4,600,000, particularly Multidrug resistant bacteria
(MDRB) high mortality caused by infecting, seriously threatens public health.Europe is annual with the U.S. because of the expenditure of bacterium infection preventing and treating
Up to 7,000,000,000 Euros and 6,500,000,000 dollars, and developing country then needs to undertake more high cost for this.MDRB is infected in the whole world
It is quick spread closely related with abuse of antibiotics and its research and development division of history into periods, i.e., new construction class is not developed between 1962 to 2000 years
The antibiotic of type；The antibacterials for having only had 3 new construction types since 2000 enter market.U.S.'s infection disease association (IDSA)
Appeal that revitalizing antibiotic researches and develops and give funded projects since 2004, intend being developed before the year two thousand twenty brand-new anti-of 10 structures
Bacterium medicine.It is expected that the research and development of anti-MDRB infection medicines will obtain fast-developing.
Acinetobacter bauamnnii (AB) is a kind of serious iatrogenic pathogen, causes respiratory tract, blood, urethra, soft tissue
And central nervous system infection, propagated by the direct or indirect way of contact between sufferer.According to 2006-2007 both at home and abroad
Nosocomial Infection Surveillance data information shows that recall rate of the Acinetobacter bauamnnii in nosocomial infection ranks forefront four, low in immunity
Under patient in, the infection of serious even lethal can be caused.It can cause Ventilator Associated Pneumonia, septicemia,
The serious infections such as meningitis, tympanitis, skin soft-tissue infection, urinary system infection contamination and central nervous system infection.
The incidence of disease and case fatality rate caused due to Acinetobacter bauamnnii infection are increased, and it is referred to as " Gram negative MRSA ".In routine
In AB infection, the incidence of MDR Acinetobacter bauamnnii (MRAB) rises to 63% in 2014 from 23% in 2004,
Its average originating rate is also significantly greater than other Gram-negative bacterias (44%vs 13%).At present, 95% MRAB is to ceftriaxone
It is resistant, 90% MRAB to Drug-resistants such as cefotaxime, lavo-ofloxacin, Meropenem, Piperacillin-Tazobactam Sodiums,
It is a great problem of clinical drug-resistant bacterium infectious disease treatment.Therefore, the novel antibacterials of screening structure are infected with tackling MRAB
The focus of new drug development will be turned into.
Antibacterial peptide (AMP) is the class small peptide being present in all organisms, with cationic and it is amphipathic the characteristics of
And various structures, it is important component that organism natural immune system is invaded anti-microbial pathogen, during biological evolution
Keep stable and efficient.So far, document has reported about 5000 AMP sequences, wherein 74 have been enter into drug development.
There is significant difference with the mechanism of action of conventional antibiotic with bacterial cell membrane as action target because AMP is main, have to MDRB
There is significant antibacterial effect, be the confrontation most potential candidate structure types of MDRB.However, natural A MP is still present ammonia
Base acid sequence is long, production cost is high, and resistance to enzyme stability is poor, degradable in vivo, and the problems such as cell dissolving toxicity, it is in clinic
Using above facing serious predicament.By chemical synthesis process obtain non-natural small molecule antibacterial peptide (sAMP), its sequence only by
3-9 amino acid residues are constituted, and due to the presence of alpha-non-natural amino acid (such as D- types amino acid or Modification of amino acid residues thing), make it
It is active significantly, simple structure, be readily synthesized, the advantage such as good stability, security are high, by the extensive pass of researcher
Note.Therefore, find that antibacterial activity is strong, resistance to enzyme stability is good by chemical synthesis process, safe sAMP and its class in vivo
It is the effective way for solving MRAB infection problems like thing.
The content of the invention
For existing problem, the first object of the present invention is to provide a kind of antibacterial hexapeptide.The second object of the present invention
It is that this kind of application of antibacterial hexapeptide is provided, the third object of the present invention is to provide a kind of antibacterial hexapeptide derivatives, the 4th mesh
Be provide the antibacterial hexapeptide derivatives application.The antibacterial hexapeptide and antibacterial hexapeptide derivatives have wide spectrum to gram-bacteria
Antibacterial activity, wherein growth of the antibacterial hexapeptide derivatives to resistance Acinetobacter bauamnnii show efficient inhibitory action, and
The small toxicity of the antibacterial hexapeptide and its derivative.
In order to realize above-mentioned first purpose, the technical scheme is that：A kind of antibacterial hexapeptide, it is characterised in that：This resists
The sequence of bacterium hexapeptide is：Arg-Arg-Trp-Trp-Arg-Trp.
In order to realize above-mentioned second purpose, the technical scheme is that：Above-mentioned antibacterial hexapeptide be applied to prepare treatment or
In the medicine of prevention bacterium infection.
In order to realize above-mentioned 3rd purpose, the technical scheme is that：A kind of antibacterial hexapeptide derivatives, its feature exists
In：The sequence of the antibacterial hexapeptide derivatives is：Arg-Arg-Trp-Trp-Arg-Trp- β-phenyl ethylamine (antibacterial peptide b).
In order to realize above-mentioned 4th purpose, the technical scheme is that：Above-mentioned antibacterial hexapeptide derivatives are applied to prepare
In the medicine for the treatment of or prevention bacterium infection.
Further：The bacterium is resistance Acinetobacter bauamnnii.Resistance Acinetobacter bauamnnii herein is sensu lato
Resistance Acinetobacter bauamnnii, including the medicine of resistance to single Acinetobacter bauamnnii and the Acinetobacter bauamnnii of resistance to multiple medicine.
Thinking of the present invention is as follows：In natural antibacterial peptide Lactoferricin B4-9On the basis of RRWQWR, combined with virtual combination
Analysis software and the websites such as storehouse designing technique, DNAstar, Bioedit, sequence logo, by finding one after test of many times
Bar has the brand-new polypeptide sequence RRWWRW (Arg-Arg-Trp-Trp-Arg-Trp) of antibacterial activity, after its C-terminal phenyl ethylamine
Still there is significant antibacterial activity.Newfound antibacterial hexapeptide and its derivative compare LfcinB4-9Bactericidal effect more preferably, without molten
Blood poison, especially its derivative show stronger bactericidal activity to resistance Acinetobacter bauamnnii, and hemolytic toxicity is small, are expected to make
It is the treatment bacterium infection especially new drug research of resistance Acinetobacter bauamnnii and exploitation.
The Pioneer Peptide synthesizers produced using application system biotech firm of the U.S. are based on the legal preparation present invention of solid phase
Disclosed antibacterial hexapeptide phenyl ethylamine trim (antibacterial peptide b) and antibacterial hexapeptide (antibacterial peptide a) and natural antibacterial peptide
Lactoferricin B4-9RRWQWR。
Detect the antibacterial of antibacterial hexapeptide of the present invention and its derivative and kill using agar hollow plate cave diffusion method and 96 well plate methods
Bacterium activity, with pre-synthesis natural antibacterial peptide Lactoferricin B4-9RRWQWR is control, carries out bactericidal activity detection,
Result shows that the bactericidal activity of antibacterial hexapeptide of the invention and its derivative is significantly stronger than the natural antibacterial peptide of control
Lactoferricin B4-9The bactericidal activity of RRWQWR.Compared with antibacterial peptide a, conditions of the antibacterial peptide b of the invention in low concentration
Just can efficiently suppress the growth of resistance Acinetobacter bauamnnii down.Can be applied to treat or prevent because of resistance Acinetobacter bauamnnii
In the medicine of the disease for causing, be such as applied to treatment cause by resistance Acinetobacter bauamnnii Ventilator Associated Pneumonia, lose
The severe infectious such as mass formed by blood stasis, meningitis, tympanitis, skin soft-tissue infection, urinary system infection contamination and central nervous system infection
In the medicine of disease.
Antibacterial peptide is also possible to act on higher organisms while efficient sterilizing includes human body cell, because antibacterial peptide
The mode of action be all on cell membrane perforation to cause that cell occurs seepage dead.So can occur red blood cell antibacterial peptide
Whether seepage is used as its virose standard, if antibacterial peptide can make the hemoglobin in red blood cell that seepage occurs, so that it may
With by detecting its OD490Value determines the size of toxicity.Experiment shows that antibacterial hexapeptide derivatives of the invention are molten in higher concentrations
Blood rate is still very low, it was demonstrated that the hemolytic toxicity of antibacterial hexapeptide derivatives of the present invention is minimum.
The beneficial effects of the invention are as follows：The antibacterial hexapeptide of engineer's synthesis that the present invention is provided and its phenyl ethylamine modification
Thing, it is convenient to obtained using solid-phase synthesis.The synthetic antibacterial peptide and its derivative are to gram-positive bacteria, Gram-negative
Bacterium has wide spectrum killing activity, and especially its derivative shows stronger antibacterial activity, hemolytic poison to resistance Acinetobacter bauamnnii
Property is minimum, can be applied in the medicine for treat or prevent the disease caused by resistance Acinetobacter bauamnnii.
Brief description of the drawings
Fig. 1 is the mass spectrogram of antibacterial hexapeptide derivatives of the present invention.
Fig. 2 is the mass spectrogram of antibacterial hexapeptide.
Specific embodiment
With reference to specific embodiment, the present invention will be further described：
Embodiment 1：
Chemical synthesis antibacterial peptide a and antibacterial peptide b and control antibacterial peptide Lactoferricin B4-9.
Antibacterial peptide a:RRWWRW(Arg-Arg-Trp-Trp-Arg-Trp)
Antibacterial peptide b:RRWWRW-PEA (Arg-Arg-Trp-Trp-Arg-Trp- β-phenyl ethylamine)
1st, the preparation of antibacterial peptide b (Arg-Arg-Trp-Trp-Arg-Trp- β-phenyl ethylamine)：
A. with 4 times of amount DMF washing resins and after being completely dried, (the piperidines of 10mL 20% is added:DMF, mass ratio) piperazine
1min is vibrated after pyridine, DMF mixed solutions and is dried, then add the (piperidines of 10mL 20%:DMF, mass ratio) piperidines, DMF mix
Close solution vibration 30min；Dry reaction container and with 4 times amount DMF washing resins, it is ensured that without piperidines residual, use ninhydrin
Check that resin particle should be blue.
B. by Fmoc protected amino acids (1mmol), 2.1mL 0.45M HBTM/HOBT (1mmol), 248uL DIEA
(2mmol) solution adds resin and vibrates 30min；Dry reaction container simultaneously measures DMF washing resins with 4 times, is checked with ninhydrin
If colourless, then prepare resin again, then continuously adding amino acid if blueness is reacted；Above-mentioned amino acid is repeated to connect
It is reversed to terminate until Peptide systhesis；After the completion of coupling, cracked with low concentration trifluoroacetic acid, precipitated with ether, sediment is added
Enter in solvent (tetrahydrofuran or its mixed solvent), then add phenyl ethylamine reaction, reaction uses high concentration trifluoro after terminating
Acetic acid Deprotection, is precipitated with ether.
C. polypeptide-resin is added to 1mL acetic acid (AcOH), 2mL trifluoroethanols (TFE) and 7mL dichloromethane (DCM)
In mixed solution, 1h is stirred at room temperature；Filtering resin and with 2 times measure TFE/DCM (volume ratios 2:8) mixed solution is rinsed, really
Protect and reclaim all products；Distillation and concentration reaction mixture is within 5mL；Added in the test tube containing the above-mentioned concentrate solutions of 100mL
Ether, checks whether the polypeptide protected completely is dissolved in ether；If insoluble, promote product to addition ice ether in test tube again
Separate out, suction filtration obtains product crude product；If dissolving, to adding water to promote product to separate out in ether, then suction filtration is produced again
Thing crude product.
D. the dried above-mentioned solid polypeptide crude products of 100mg are weighed, the trifluoroacetic acids of 10mL 0.1% (TFA), sample is dissolved in
After with 0.22 μm of membrane filtration, isolated and purified on RPLC (RP-HPLC)；Eluent is 0.1%TFA water
Solution (A) and 0.1% acetonitrile (ACN) solution (B), elution requirement are 0-60%B gradient elution 30min, collect eluting peak and put
The freeze-drying in freeze dryer (- 50 DEG C)；Purify dried antibacterial peptide HPLC and determine purity and detected with mass spectrum (MS) and divide
Protonatomic mass is consistent with the molecular weight of theoretical calculation.Antibacterial peptide symthesis, purifying, the identification experiment of this paper are in Shanghai purple domain biotechnology
Co., Ltd completes.
2nd, antibacterial peptide a and antibacterial peptide Lfcin B4-9The preparation of RRWQWR
According to Fmoc solid phase procedures artificial synthetic antimicrobial peptide a and antibacterial peptide the Lactoferricin B of standard4-9, synthetic peptide
Inverted HPLC (2.2 × 25cm of Vydac 218TP1022 posts) purifying, using acetonitrile/water/trifluoroacetic acid system elutions,
MALDI-TOF and EPI mass spectral analyses.Antibacterial peptide symthesis are by Shanghai Zi Yu bio tech ltd.
Embodiment 2
The antibacterial activity detection of antibacterial peptide
Various reference cultures used below are purchased from Guangdong Province's Culture Collection, and drug-fast bacteria is by the 3rd medical officer
University provides.
The antibacterial activity of synthetic antibacterial peptide b and antibacterial peptide a is detected using agar plate diffusion method, and uses natural antibacterial
Peptide Lfcin B4-9As control, to evaluate the bactericidal activity of antibacterial peptide b and antibacterial peptide a in the present invention.
The antibacterial activity of antibacterial peptide is measured according to the following steps：
A. strain recovery：With oese distinguish picking appropriate Escherichia coli, staphylococcus aureus, Acinetobacter bauamnnii,
Pseudomonas aeruginosa, enterococcus faecalis, MRSA, the medicine of resistance to single Acinetobacter bauamnnii (to cefotaxime resistance, similarly hereinafter), multidrug resistant
Acinetobacter bauamnnii (to gentamicin and cefotaxime resistance simultaneously, similarly hereinafter) is rule in respective culture medium, mark.37 DEG C of perseverances
Temperature culture carton upside down culture (12-16h).
B. Spawn incubation：Single bacterium colony to 100ml liquid MHB nutrient solutions is selected respectively, puts 37 DEG C, 160 turns, shaking table culture
(12-16h)。
C. prepared by bacteria suspension：The turbidity of bacteria suspension is prepared in 0.5 Maxwell turbidity or so, now bacteria colony count is about 1.5
×108Cfu/ml, then presses 1 again:1000 are diluted to 105-106The bacteria suspension of cfu/ml.
D. bacteriostatic experiment：Escherichia coli, staphylococcus aureus, Acinetobacter bauamnnii, the P. aeruginosa that will have been diluted
Bacterium, enterococcus faecalis, MRSA, the medicine of resistance to single Acinetobacter bauamnnii, Multi-drug resistant Acinetobacter baumannii bacteria suspension press 0.2ml/ respectively
The amount of flat board (plate diameter is 150mm) is uniformly applied to 40mL solid LB medias；After culture medium solidifies completely, punch diameter
6/flat boards of 8mm, labeled as +/-/CAZ/A/B/C, represent positive control (gentamicin), negative control (deionization respectively
Water), cefotaxime, (A is antibacterial peptide a for three polypeptides；B is antibacterial peptide b；C is LfcinB64-9)."+" hole adds 50ul 1mg/ml
Gentamycin solution；"-" hole adds 50 μ l deionized waters；" CAZ " hole adds 50ul 1mg/ml cefotaxime solution；Distinguish in A/B/C holes
Plus 50ul 1mg/ml antibacterial peptide solutions.After 4 DEG C stand 3h, 37 DEG C of constant incubator cultures observe naked eyes inhibition zone big after 12h
It is small and determine antibacterial circle diameter.Every peptide independently carries out 3 experiments under every kind of strain.
Antibacterial activity of the 1mg/ml antibacterial peptides of table 1 to different bacterium
Note：CAZ- cefotaximes；"-" is indicated without obvious inhibition zone
Find out antibacterial peptide b of the invention and antibacterial peptide a sterilizing abilities substantially and better than natural antibacterial peptide from upper table 1.
The bacteriostatic activity detection of the synthetic antibacterial peptide of embodiment 3
Various reference cultures used below are purchased from Guangdong Province's Culture Collection, and drug-fast bacteria is by the 3rd medical officer
University provides.
The bactericidal activity of synthetic antibacterial peptide is detected using 96 well plate methods, and with natural antibacterial peptide Lfcin B4-9Make
It is control, to evaluate the bacteriostatic activity of antibacterial peptide a, b.
The bacteriostatic activity of antibacterial peptide is measured according to the following steps：
A. by Escherichia coli, staphylococcus aureus, Acinetobacter bauamnnii, pseudomonas aeruginosa, enterococcus faecalis, MRSA,
The medicine of resistance to single Acinetobacter bauamnnii, Multi-drug resistant Acinetobacter baumannii incubated overnight, picking list on sterilizing NA culture medium flat plates
Colony inoculation cultivates 18~24h in sterilizing MHB nutrient solutions, 37 DEG C of 170r/min.
B. the bacterium solution after culture is diluted to 105-106The bacteria suspension of cfu/ml.There to be the peptidomimetic to be measured of bacteriostatic activity respectively
Solution by adding 96 hole microtest plates after 2 times of serial dilutions, leave a blank without (avoiding edge effect from causing by the 1st hole and the 12nd hole
Make the data inaccurate).In addition to the 2nd hole adds dilution bacterium solution 160 μ l, each holes of 3-9 add 100 μ l, after in the 2nd hole addition antibacterial
Peptide stoste (the μ g/ml of concentration 1280) 40 μ l, are suctioned out in the 3rd hole of 100 μ l additions after mixing, and the 9th hole is diluted to successively, discard 100 μ
l.The final concentration of antibacterial peptidomimetic so to be measured is respectively:
Take the peptidomimetic to be measured that concentration is 1280 μ g/ml and be diluted to following concentration (μ g/ml)：
| Numbering | A2 | A3 | A4 | A5 | A6 | A7 | A8 | A9 |
| Concentration | 256 | 128 | 64 | 32 | 16 | 8 | 4 | 2 |
10th hole growth control, the 11st hole is positive control (Imipenem), plus 160 μ l bacterium solutions and 40 μ l are with concentration antibiosis
100 μ l are abandoned after plain solution mixing.Each antibacterial peptide is parallel to be done 3 times.After cultivating 16h in 37 DEG C, surveyed respectively with ELISA ELIASAs
OD600Value, minimum OD600The corresponding Cmin of value is just the MIC value of the antibacterial peptide.Antibacterial peptide a, b difference are calculated accordingly
To Escherichia coli, staphylococcus aureus, Acinetobacter bauamnnii, pseudomonas aeruginosa, enterococcus faecalis, MRSA, the medicine of resistance to single Bao
The MIC of graceful acinetobacter calcoaceticus, Multi-drug resistant Acinetobacter baumannii.
Minimal inhibitory concentration (MIC) of the antibacterial peptide of table 2 to different bacterium
Minimal inhibitory concentration value in upper table is smaller, then represent antibacterial ability stronger.Synthetic antibacterial peptide a and b of the invention
MIC than Lfcin B4-9It is intended to small, the antibacterial ability of synthetic antibacterial peptide a and b is much stronger than antibacterial peptide Lfcin B4-9But, resist
Bacterium peptide b especially to drug-resistant bacteria Acinetobacter bauamnnii bactericidal effect more preferably.
The hemolysis in vitro Activity determination of embodiment 4
The present embodiment is used to detect that whether synthetic antibacterial peptide has hemolytic activity, and use mechanochemical method to human erythrocyte
Antibacterial peptide a and antibacterial peptide the Lfcin B of synthesis4-9As control.The blood sample for using is taken at aseptic Sheep Blood.
The detecting step of hemolytic activity is：
A. aseptic Sheep Blood is centrifuged 5min 3000rpm/min, and is rinsed 3 times with PBS, repeated centrifugation operation,
Abandoning supernatant, retains red blood cell.
B.0.1ml red blood cell liquid 9.9ml PBS liquid dilutes (red blood cell ultimate density is 1%), and concentration is taken respectively is
512nd, the μ l of antibacterial peptide 200 and 200 μ l the dilution red blood cell liquid of 256,128,64,32,16,8 μ g/ml are incubated 1 after mixing at 37 DEG C
Hour, then it is centrifuged 5 minutes in 4000rpm/min, take suspension and be transferred to 96 hole elisa plates and respectively in the inspection of 414nm wavelength
The light absorption value of suspension is surveyed, the hemolysis rate per hole is calculated.The PBS of 0.01mol/L is used as negative control, 0.1%Triton-X
100 (Triton X-100s) are used as positive control.Hemolysis rate (%)=(developmental tube absorbance-negative control pipe extinction
Degree)/(positive control pipe absorbance-negative control pipe absorbance) × 100%.
C. hemolysis rate experiment is with antibacterial peptide a and Lfcin B4-9It is control, independent three repetitions are tested.
4 three kinds of antibacterial peptide haemolysis promoting blood circulation testing results of table
The hemolysis rate value of antibacterial peptide is smaller, then the hemolytic toxicity for representing antibacterial peptide is smaller.Result can be seen that anti-from table
The hemolytic toxicity of bacterium peptide a, b is all below 5%, even if the increase of its hemolytic toxicity is not also obvious in the case of concentration is elevated.
It is very low compared to control natural antibacterial peptide hemolytic toxicity, there is not significantly haemolysis in higher concentrations particularly,
It is the important foundation of next step patent medicine.
<210> 1
<211>6
<212> PRT
<213>It is artificial synthesized
<220>
<223>Antibacterial peptide a
<400> 1
Arg-Arg-Trp-Trp-Arg-Trp
1 5 6
<210> 1
<211>6
<212> PRT
<213>It is artificial synthesized
<220>
<223>Antibacterial peptide b
<400>2
Arg-Arg-Trp-Trp-Arg-Trp- β-phenyl ethylamine
1 5 6
Claims (5)
1. a kind of antibacterial hexapeptide, it is characterised in that：The sequence of the antibacterial hexapeptide is：Arg-Arg-Trp-Trp-Arg-Trp.
2. the application of antibacterial hexapeptide described in claim 1, it is characterised in that：It is applied to the medicine for preparing treatment or prevention bacterium infection
In thing.
3. a kind of antibacterial hexapeptide derivatives, it is characterised in that：The sequence of the antibacterial hexapeptide derivatives is：Arg-Arg-Trp-Trp-
Arg-Trp- β-phenyl ethylamine.
4. the application of antibacterial hexapeptide derivatives described in claim 3, it is characterised in that：It is applied to prepare treatment or pre- bacteriological protection sense
In the medicine of dye.
5. application of the antibacterial hexapeptide derivatives in Antibacterial is prepared according to claim 4, it is characterised in that：It is described
Bacterium is resistance Acinetobacter bauamnnii.
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| CN113544139A (en) * | 2019-02-28 | 2021-10-22 | 丹迪生物科技有限公司 | Polypeptide having antibacterial activity, composition for preventing or treating sepsis comprising the same, and antibacterial composition |
| CN113999285A (en) * | 2021-12-02 | 2022-02-01 | 浙江大学 | Antibacterial heptapeptide and application thereof |
| CN115746094A (en) * | 2022-10-25 | 2023-03-07 | 重庆理工大学 | Antibacterial peptide and preparation method and application thereof |
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| CN113544139A (en) * | 2019-02-28 | 2021-10-22 | 丹迪生物科技有限公司 | Polypeptide having antibacterial activity, composition for preventing or treating sepsis comprising the same, and antibacterial composition |
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