CN103319568A - Non-protein amino acid antibacterial peptide and application for same - Google Patents
Non-protein amino acid antibacterial peptide and application for same Download PDFInfo
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- CN103319568A CN103319568A CN2013102466355A CN201310246635A CN103319568A CN 103319568 A CN103319568 A CN 103319568A CN 2013102466355 A CN2013102466355 A CN 2013102466355A CN 201310246635 A CN201310246635 A CN 201310246635A CN 103319568 A CN103319568 A CN 103319568A
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Abstract
The invention discloses a non-protein amino acid antibacterial peptide. The antibacterial peptide has any one sequence in the following sequence tables: SEQ ID NO. 1: R-FPA-R-FPA-EtBn; SEQ ID NO. 2: R-BTF-R-BTF-EtBn; SEQ ID NO. 3: R-FPA-R-EtBn; SEQ ID NO. 4: R-Nag-R-EtBn. The four antibacterial peptides disclosed by the invention are good in structure specificity, strong in in-vivo anti-enzymolysis capacity, definite in action mechanism, low in toxic and side effects, easy in chemical synthesis, and have a medicine-forming potential. The invention further discloses an application for the antibacterial peptides.
Description
Technical field
The invention belongs to non-protein amino acid antibacterial peptide and the application thereof in antibacterial peptide field, particularly a kind of artificial design.
Background technology
Current antibiotic resistance with day strengthen, particularly antibiotic abuse is on the rise, the mankind need badly and develop that a class is efficient, the novel antibacterial medicine of low toxicity, noresidue.And the antibacterial peptide antibacterial peptide has caused that with biological activity and the particular mechanism of action that it differs from traditional antibiotic uniqueness people greatly pay close attention to, it has, and has a broad antifungal spectrum, good stability, side effect are little, the advantage such as have no drug resistance, the serial difficult problems such as the resistance that is expected to overcome current antibacterials is strong, side effect is large, scientists think that it is expected to become antibiotic, antiviral, the anticancer medicine of a new generation.
Antibacterial peptide (antibacterial peptides, ABP) be called again antimicrobial peptide (anti-microbacterial peptides, AMP) be organism to external world the cause of disease material infect and produce have the opposing extraneous a series of immune responses product, eliminate a class biological activity micromolecule polypeptide of vivo mutations cell, generally formed by 12-50 amino-acid residue, contain clean positive charge and 50% above hydrophobic residue.Antibacterial peptide not only can act on bacterium, fungi, protozoon, virus and tumour cell etc., also has simultaneously the ability of enhancing body immunity and accelerating wound healing.Antibacterial peptide has stronger stability under larger ionic strength and lower or higher pH value condition.Simultaneously, have faster sterilizing ability, be difficult for to produce resistance, do not find so far the resistance phenomenon that caused by antibacterial peptide, and the antibacterial peptide of these natural origins is without teratogenesis and can not produce accumulate poisoning.At present, have multiple Antimicrobially active polypeptides molecular designing and remodeling method for antibacterial peptide research, be desirably in and improve stability in its blood plasma of further raising of anti-microbial activity while, reduce toxic side effect, and then lay the foundation for antibacterial peptide enters clinical application.
Summary of the invention
The purpose of this invention is to provide a kind of non-protein amino acid antibacterial peptide, introduce the method for design of alpha-non-natural amino acid on the design concept basis of small molecules cationic antibacterial peptide, peptide chain is shorter, and every polypeptide peptide chain is no more than 4 amino-acid residues, so that easily synthetic; Electric charge is high, and every design polypeptide is with two positive charges at least; Amphipathic strong, guarantee that it has low hemolytic toxicity; Advantage amino acid is many; And the peptide chain end is flexible, the ethylbenzene amination protection that hydrophobicity is strong.(simultaneously, realize its high flux screening by the quantitative structure-activity relation analysis, saved time and the cost of novel antimicrobial peptide design with screening, improved reasonableness and the feasibility of antibacterial peptide molecular designing.) 4 antibacterial peptide structure specificitys of the present invention are good, the interior resistance to enzymolysis ability of body is strong, the mechanism of action is clear and definite, toxic side effect is little, chemosynthesis is easy, have the patent medicine potentiality.The present invention also provides the application of described antibacterial peptide.
In order to reach above purpose, the present invention adopts following technical scheme:
A kind of non-protein amino acid antibacterial peptide, described antibacterial peptide have in the following sequence table sequence of any one:
SEQ ID NO.1:R-FPA-R-FPA-EtBn;
SEQ ID NO.2:R-BTF-R-BTF-EtBn;
SEQ ID NO.3:R-FPA-R-EtBn;
SEQ ID NO.4:R-Nag-R-EtBn。
FPA：
BTF：
Nag：
Design based on the antibacterial peptide storehouse, the relevant information that considers structure activity relationship, advantage amino acid, advantage site and secondary structure trend finds in most cationic antimicrobial peptide sequences, and the arginine R that possesses its positive charge and the hydrophobic tryptophane W of contribution are the amino acid of its advantage.This research is simplified sequence in an enterprising step of antibiotic six peptides basis, only keeps this two optimum amino acid, carries out on this basis transformation and the modification finishing screen of alpha-non-natural amino acid and elects 4 plan peptides.
Antibacterial peptide C holds amidated processing, helps the increase of static charge of peptide and the stability of antibacterial peptide, and the cationic of intending peptide is strengthened, and has increased the bacteriostatic activity of antibacterial peptide and the guarantee of stability.Antibacterial peptide N end also will help to improve the activity of antibacterial peptide without unnecessary residue.
The Fmoc solid state chemistry synthetic schemes of employing standard namely prepares peptide by going to protect and activate crosslinked two reaction iterative cycles synthetic the most at last.Synthetic polypeptide crude product carries out purifying at high pressure liquid chromatograph (HPLC), and purifying is selected the C18 preparative column, and purity reaches more than 95%.Product behind the purifying carries out the evaluation of analyzing molecules amount, charge distribution, purity and quality through reversed-phase liquid chromatography instrument (RP-HPLC) and mass spectrum (MS) respectively.
The secondary structure of described 4 antibacterial peptides:
SEQ ID NO.1:
SEQ ID NO.2：
SEQ ID NO.3：
SEQ ID NO.4：
The application of antibacterial peptide:
The application of described SEQ ID NO.1 in the medicine that suppresses MRSA, streptococcus aureus, intestinal bacteria and Pseudomonas aeruginosa.
The application of described SEQ ID NO.2 in the medicine that suppresses MRSA, streptococcus aureus, intestinal bacteria and Pseudomonas aeruginosa.
The application of described SEQ ID NO.3 in the medicine that suppresses intestinal bacteria and Pseudomonas aeruginosa.
The application of described SEQ ID NO.4 in suppressing enterococcus faecalis and colibacillary medicine.
The beneficial effect of the described technology of the application is:
4 antibacterial peptide peptide chains of the present invention are shorter, and every polypeptide peptide chain is no more than 4 amino-acid residues, so that easily synthetic; Electric charge is high, and every design polypeptide is with two positive charges at least; Amphipathic strong, guarantee that it has low hemolytic toxicity; Advantage amino acid is many; And the peptide chain end is flexible, the ethylbenzene amination protection that hydrophobicity is strong.Article 4, antibacterial peptide structure specificity is good, the interior resistance to enzymolysis ability of body is strong, the mechanism of action is clear and definite, toxic side effect is little, chemosynthesis is easy, have the patent medicine potentiality.
Description of drawings
Fig. 1 is the HPLC figure of SEQ ID NO.1 among the embodiment 2.
Fig. 2 is the MS figure of SEQ ID NO.1 among the embodiment 2.
Fig. 3 is the HPLC figure of SEQ ID NO.2 among the embodiment 2.
Fig. 4 is the MS figure of SEQ ID NO.2 among the embodiment 2.
Fig. 5 is the HPLC figure of SEQ ID NO.3 among the embodiment 2.
Fig. 6 is the MS figure of SEQ ID NO.3 among the embodiment 2.
Fig. 7 is the HPLC figure of SEQ ID NO.4 among the embodiment 2.
Fig. 8 is the MS figure of SEQ ID NO.4 among the embodiment 2.
Embodiment
Below in conjunction with embodiment foregoing invention content of the present invention is described in further detail.
But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.Not breaking away from the above-mentioned technological thought situation of the present invention, according to ordinary skill knowledge and customary means, make various replacements and change, all should comprise within the scope of the invention.
Embodiment 1:
The present embodiment is the design of described antibacterial peptide and synthesizes:
1, the antibacterial peptide in the existing antibacterial peptide database (APD2) is carried out the primary sequence compare of analysis, determine the sequence pattern of cationic antibacterial peptide;
2, existing cationic antibacterial peptide is carried out Quantitative Structure-Activity Relationship Study, determine advantage amino acid and the chemical modification method thereof of core sequence;
3, based on amino acid and the chemically modified thereof in sequence pattern, advantage site, the antibacterial peptide storehouse that virtual generation structure is various;
4, based on structure activity relationship analytical results screening and synthesize;
5, filter out designed best antibacterial peptide by anti-microbial activity, cytotoxicity, plasma stability examination.
Above SEQ ID NO.1, SEQ ID NO.2 and SEQ ID NO.3 are synthetic in the biochemical company limited of Shanghai gill; beautiful high chemical company limited synthesizes SEQ ID NO.4 in Shanghai; all adopt the Fmoc solid state chemistry synthetic schemes of standard, prepare the most at last peptide by going to protect and activate crosslinked two reaction iterative cycles synthetic.
The purifying of gained polypeptide, analysis and identification: the synthetic polypeptide crude product of above-mentioned steps carries out purifying at Delta600 type high pressure liquid chromatograph (HPLC), and purifying is selected the C18 preparative column, and purity reaches more than 95%.
Embodiment 2:
The present embodiment is the structural confirmation of described antibacterial peptide:
The designed peptide of preparation is analyzed through mass spectrum (MS), and it shows that in mass spectrum the molecular weight that calculates and the error maximum between the peptide sequence theoretical molecular about 1/ ‰, prove that the polypeptide for preparing is the antibacterial peptide of design.Detect its purity through RPLC and all (seeing Table 1) more than 95%, it is for subsequent use that the peptide of accredit is intended product.
The mass spectroscopy of table 1 synthetic peptide and purity
HPLC and MS data are seen Fig. 1-8.
Embodiment 3:
The present embodiment is the activity experiment of described antibacterial peptide:
Experimental procedure:
A. activate bacterium: the solid LB nutrient solution of 2 bottles of 150ml of preparation, the liquid LB nutrient solution of 4 bottles of 100ml is with the equipment instrument high-temp steam sterilizing 30min such as culture dish.4 of solid LB nutrient solution a kind of rhyme scheme in Chinese operas serving as the prelude to a complete score for voices respectively from being kept at-20 ℃ enterococcus faecalis, streptococcus aureus, MRSA and pseudomonas aeruginosa, Escherichia coli bacteria liquid picking, and are rule respectively mark with transfering loop separately at flat board.Be inverted overnight incubation (12-16h) in 37 ℃ of constant incubators.
B. culturing bacterium: select single bacterium colony to 100ml liquid LB nutrient solution, put 37 ℃, 170 turn, shaking table overnight incubation (12-16h).
C. bacteriostatic activity experiment: with enterococcus faecalis, streptococcus aureus, MRSA, pseudomonas aeruginosa and intestinal bacteria are mixed with respectively 10
5-10
6The bacteria suspension of cfu/ml, bacterium liquid evenly is applied to 40ml solid LB substratum by the amount of 0.2ml/ dull and stereotyped (plate diameter is 150mm); After substratum solidifies fully, diameter 8mm10/flat board of punching, respectively mark positive control (gentamicin), negative control (deionized water), and 4 designs intend peptides.Above-mentioned compound experiment purity is reached antibacterial peptide more than 95%, is dissolved as concentration 1mg/ml(DMSO concentration＜5 ‰ through the phosphate buffered saline buffer (PBS) of dimethyl sulfoxide (DMSO) (DMSO) and 0.01mol/L) be used for the experiment of bacteriostatic activity checking.The positive control hole adds 50 μ l1mg/ml gentamicins; Negative control hole adds 50 μ l deionized waters; Article 4, design plan peptide hole adds respectively 50 μ l1mg/ml and intends peptide solution.4 ℃ leave standstill 3h after, 37 ℃ of constant incubators are cultivated, and observe naked eyes inhibition zone size behind the 7h and measure antibacterial circle diameter.Intend peptide for every and under every kind of bacterial classification, independently carry out 3 experiments.
Wherein synthetic plan peptide SEQ ID NO.1 and SEQ ID NO.2 has obvious bacteriostatic activity to MRSA, streptococcus aureus, intestinal bacteria and Pseudomonas aeruginosa, SEQ ID NO.3 has obvious restraining effect to intestinal bacteria and Pseudomonas aeruginosa, and SEQ ID NO.4 then has obvious inhibition zone to enterococcus faecalis and intestinal bacteria.
Embodiment 4:
The present embodiment is the bacteriostatic activity stability experiment of described antibacterial peptide:
The flat board of embodiment 3 experiments is continued to be positioned over 37 ℃ of constant incubators, one week of lasting cultivation, observe once every 12h, sterilization time length length is judged in the variation of record inhibition zone within 7 days.
Experiment shows that the inhibition zone of intending peptide SEQ ID NO.1 and positive control gentamicin dwindles, and forms the more shallow concentric(al) circles of color after cultivating 10 hours.This is likely along with the outside diffusion concentration of liquid reduces gradually.After being contracted to the 16mm size, inhibition zone in following 3 days, no longer changes.Although the plan peptide SEQ ID NO.1 sterilizing ability of these change list exposed installation meters is strong, can not bacteria growing inhibiting when concentration is low, can property continue the long period and Comparison of effect on sterilization is stable in effective bacteriocidal concentration.
Although it is less to intend the inhibition zone diameter of peptide SEQ ID NO.2, continue to cultivate no longer and change, its sterilization stability is described better, or its lower penetrating power makes it keep higher drug level in certain limit, thereby can continue sterilization.
Intend peptide SEQ ID NO.3 and SEQ ID NO.4 inhibition zone and become irregular after continuing one day, inhibition zone also has dwindling in various degree, but process is comparatively slow, and just no longer changes after inwardly dwindling 1mm.Show that the sterilization persistence is better.
Embodiment 5:
The present embodiment is minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) determination experiment of described antibacterial peptide:
Adopt micro-multiple By Dilution.
Minimal inhibitory concentration MIC (Minimal inhibitory concentration) is exactly the Cmin of energy bacteria growing inhibiting.Objective checking medicine bacteriostatic activity index is usually measured MIC in the antibacterial medicines screening experiment
50The drug level that namely can suppress 50% bacterial growth.MIC
50Bacteriostasis rate by one group of concentration gradient calculates according to computational tool.Inhibiting rate=[1-(experimental group-positive control)/(growth control-positive control)] * %.Minimal bactericidal concentration MBC (Minimal bactericidal concentration) is exactly the minimum concentration that can suppress the plan peptide of any remaining colony growth fully.
Experimental procedure:
A. with enterococcus faecalis, streptococcus aureus, MRSA and intestinal bacteria, pseudomonas aeruginosa incubated overnight on sterilization LB culture medium flat plate, picking list colony inoculation is in the LB nutrient solution of sterilization Erlenmeyer flask, and 37 ℃ of 170r/min cultivate 12h.
B. the bacterium liquid after will cultivating is done the 1:1000 dilution (makes the bacterium number reach 10
5～10
6Cfu/ml).The plan peptide solution to be measured that bacteriostatic activity will be arranged respectively adds in the 96 hole microtest plates after by 2 times of serial dilutions, and leaving a blank in the 1st hole and the 12nd hole need not (avoids edge effect cause data inaccurate).Except the 2nd hole added dilution bacterium liquid 160 μ l, each hole of 3-9 all added 100 μ l, continues to add antibiotic plan peptide stoste (concentration 1280 μ g/ml) 40 μ l in the 2nd hole, and sucking-off 100 μ l add in the 2nd hole after mixing, and are diluted to successively the 9th hole, discard 100 μ L.The whole mass concentration of antibiotic plan peptide to be measured like this is respectively:
The plan peptide dilution to be measured of getting concentration and be 1280 μ g/m L is following concentration (μ g/ml):
A2 A3 A4 A5 A6 A7 A8 A9
256 128 64 32 16 8 4 2
The 10th hole growth control, the 11st hole positive contrast (gentamicin) add abandons 100 μ l after 160 μ l bacterium liquid and 40 μ l mix with the concentration antibiotic solution.37 ℃ cultivate 16h after, under 600nm, survey respectively OD value with the ELISA microplate reader, calculate the plan peptide respectively to the MIC of streptococcus aureus, intestinal bacteria, pseudomonas aeruginosa, methicillin resistant staphylococcus aureus and enterococcus faecalis
50
C. intend peptide MIC
50Determine intend peptide concentration calculating according to the minimum that the muddy degree than control wells (11 hole) is lower than 50% or more.Intend peptide to the MIC of every kind of bacterium liquid for every
50 Independent test 3 times is averaged.
D. getting 10 μ l in the content from the minimum plate well that does not have a bacterial growth and be applied on the LB agar plate, cultivate 18h for 37 ℃, whether have colony growth, determine the minimal bactericidal concentration (MBC) of plan peptide with this if observing.
Article 4, intend peptide and respectively streptococcus aureus, MRSA, intestinal bacteria, pseudomonas aeruginosa, enterococcus faecalis are measured MIC and MBC at microplate reader 600nm.Intend peptide to the MIC independent test of every kind of bacterium liquid 3 times for every, average and determine to intend respectively MIC and the MBC of peptide, see Table 2 and table 3.Find out from table, no matter be gram-positive microorganism or Gram-negative bacteria, the antibacterial ability of designed peptide has good effect.The concentration value of BMC should be in the upper hole that MIC50 occurs in theory, and still because the concentration gradient scope that this experiment arranges is lower, the BMC of the peptide that SEQ ID NO.3 and SEQ ID NO.4 minimum inhibitory concentration are higher does not drop in the concentration range.Further the weak peptide BMC mensuration of these bacteriostatic activities is had little significance, therefore do not consider.
4 kinds of plans of table 2 peptide to different bacterium anti-microbial activity MIC50 relatively
4 kinds of plans of table 3 peptide to different bacterium anti-microbial activity minimal bactericidal concentration (MBC) relatively
"-" is illustrated in maximum concentration does not have complete killing bacteria.
Embodiment 6:
The present embodiment is the hemolytic toxicity experiment of described antibacterial peptide:
In the safety evaluation of medicine, it is an important index that hemolytic is measured, if produce haemolysis, proves that medicine has serious toxic reaction to body.Erythrocyte has certain resistibility to hypotonic solution, is referred to as erythrocytic osmotic fragility.When the NaCl strength of solution is low to 0.42%～0.46% the time, some red corpuscle is broken because of overplumping, oxyphorase is overflowed in red corpuscle, and this phenomenon is called haemolysis.When the NaCl strength of solution is low to 0.32%～0.34% the time, then all haemolysis all occurs in red corpuscle.Whether antibacterial peptide has inhibitory or killing effect to the human normal cell, namely whether has cytotoxic effect, is that can the decision antibacterial peptide research and develop one of key factor that becomes medicine.
Experimental procedure:
A. with the centrifugal 10min3000rpm/min of Sheep Blood and with PBS damping fluid (10mM138mM NaCl and2.7mM KCL, PBS pH7.4) flushing 3 times, abandon supernatant, only remaining red corpuscle.
B.0.1ml red corpuscle liquid is at 9.9ml PBS liquid dilution (the red corpuscle ultimate density is 1%) 200 μ l and 640,320,160,80,40,20(μ g/ml) the antibiotic plan peptide 200 μ l of various concentration hatched 1 hour at 37 ℃, then at 4000rpm/min centrifugal 5 minutes, get the light absorption value that suspension is transferred to 96 hole elisa plates and detected respectively suspension at the 414nm wavelength, calculate hemolysis rate and the LD50 value in every hole.0.01mol/L PBS as negative control, 0.1%Triton-X100 (Triton X-100) is as positive control.Hemolysis rate (%)=(developmental tube absorbancy-negative control pipe absorbancy)/(positive control pipe absorbancy-negative control pipe absorbancy) * 100%[62].The hemolysis rate value of antibacterial peptide is less, and the hemolytic toxicity that then represents antibacterial peptide is less.
4 kinds of antibacterial peptide hemolysis rates of table 4
Embodiment 7:
The present embodiment is the plasma stability experiment of described antibacterial peptide:
The stability of antibacterial peptide in blood plasma has material impact to its actual antibacterial ability.If antibacterial peptide too easily enzymolysis does not just become the property of medicine.This experiment adopts RPLC to detect its residual concentration behind external and blood plasma reaction different time, recently calculates its transformation period in blood plasma according to the percentage of peak area.
A. 4 peptides are formulated as 1mg/ml solution with deionized water respectively; The deactivation diluted plasma is that 25% concentration is for subsequent use.
B. get the aseptic dry EP pipe of 1.5ml and be labeled as successively A0, A1, A2, A3, A4, A5, A6, A0 represents blank, namely adds peptide solution and 200 μ l deionized waters that 200 μ l configure, adds 600 μ l acetonitriles again.The every pipe of A1-A6 adds peptide solution and the 200 μ l blood plasma for subsequent use that 200 μ l configure, and makes medicine and plasma concentration ratio be 1:1.A1-A6 represents the reaction times point that experimental group is different, be followed successively by 0.5,1,1.5,2,2.5,3(h).6 groups of experimental group EP pipes except A0 are put into 37 ℃ of water-baths suspension heating.Timing was taken out A1 after 5 minutes, and adding immediately 600 μ l(, to make cumulative volume be 1ml) the acetonitrile termination reaction, then put into 4 ℃ of refrigerators and made reaction terminating complete in 20 minutes.Take out A2 after 10 minutes, repeat successively aforesaid operations, until took out A6 on the 30th minute, add the acetonitrile termination reaction and 4 ℃ leave standstill 20 minutes after at the centrifugal 15min of 12000r/min, draw 500 μ l supernatant liquors and detect with the efficient liquid phase chromatographic analysis instrument.
C. Agilent1220 type high performance liquid chromatograph and Welch Ultimate XB-C18 chromatographic column, moving phase: A liquid: DDW+0.1%TFA, B liquid: acetonitrile+0.1%TFA are adopted in stratographic analysis; Flow velocity: 1.0ml/min; Detect ripple 220nm; Column temperature: room temperature; Gradient method; 0min B liquid 15%, 30min B liquid 45%, 30.1min B liquid 100%, 31min B liquid 100%, 37min Stop.
D. will with the peak area integration of the identical retention time of blank, be the peak area under each time point drug level, in the HPLC chromatograms is analyzed, under the same terms, the concentration height is directly proportional with the peak area size, so we establish the peak area of blank is 100%, the ratio of the peak area of all the other experimental group and blank peak area is exactly the per-cent of its concentration.The concentration of each time point of according to the method experiment with computing group.The independent triplicate of above experiment, the calculating of averaging.
The result shows, the plasma stability of the plan peptide that this Subject Design is synthetic improves a lot compared to the natural amino acid antibacterial peptide.The non-natural transformation of proof antibacterial peptide can improve its plasma stability to a great extent.
In sum, 4 antibacterial peptide structure specificitys of the present invention are good, the interior resistance to enzymolysis ability of body is strong, the mechanism of action is clear and definite, toxic side effect is little, chemosynthesis is easy, have the patent medicine potentiality.
Sequence table
＜110〉Chongqing University of Technology
＜120〉a kind of non-protein amino acid antibacterial peptide and application thereof
<160>4
<170>PatentIn Version3.1
<210>1
<211>4
<212>PRT
＜213〉artificial design
<220>
<222>（1）…（4）
<400>1
R FPA R FPA EtBn
1
<210>2
<211>4
<212>PRT
＜213〉artificial design
<220>
<222>（1）…（5）
<400>2
R BTF R BTF EtBn
1 5
<210>3
<211>3
<212>PRT
＜213〉artificial design
<220>
<222>（1）…（3）
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R FPA R EtBn
1
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<212>PRT
＜213〉artificial design
<220>
<222>（1）…（3）
<400>3
R Nag R EtBn
1
Claims (5)
1. non-protein amino acid antibacterial peptide is characterized in that: described antibacterial peptide has in the following sequence table sequence of any one:
SEQ ID NO.1: R-FPA-R-FPA-EtBn;
SEQ ID NO.2: R-BTF-R-BTF-EtBn;
SEQ ID NO.3: R-FPA-R-EtBn;
SEQ ID NO.4: R-Nag-R-EtBn。
2. the application of a non-protein amino acid antibacterial peptide claimed in claim 1 is characterized in that: the application of described SEQ ID NO.1 in the medicine that suppresses MRSA, streptococcus aureus, intestinal bacteria and Pseudomonas aeruginosa.
3. the application of a non-protein amino acid antibacterial peptide claimed in claim 1 is characterized in that: the application of described SEQ ID NO.2 in the medicine that suppresses MRSA, streptococcus aureus, intestinal bacteria and Pseudomonas aeruginosa.
4. the application of a non-protein amino acid antibacterial peptide claimed in claim 1 is characterized in that: the application of described SEQ ID NO.3 in the medicine that suppresses intestinal bacteria and Pseudomonas aeruginosa.
5. the application of a non-protein amino acid antibacterial peptide claimed in claim 1 is characterized in that: the application of described SEQ ID NO.4 in suppressing enterococcus faecalis and colibacillary medicine.
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| CN201310246635.5A CN103319568B (en) | 2013-06-20 | 2013-06-20 | Non-protein amino acid antibacterial peptide and application for same |
| CN201410674665.0A CN104478993B (en) | 2013-06-20 | 2013-06-20 | A kind of non-protein amino acid antibacterial peptide and its application |
| CN201410674290.8A CN104371002B (en) | 2013-06-20 | 2013-06-20 | A kind of non-protein amino acid antibacterial peptide and its application |
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| CN201410674665.0A Division CN104478993B (en) | 2013-06-20 | 2013-06-20 | A kind of non-protein amino acid antibacterial peptide and its application |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1300293A (en) * | 1998-03-16 | 2001-06-20 | 阿斯特拉曾尼卡有限公司 | Process for the preparation of a tetrapeptide |
| CN101293925A (en) * | 2007-04-29 | 2008-10-29 | 王鹤尧 | Preparation and application of synthetic polypeptide medicaments for treating tubercle bacillus infection contamination |
| CN101319007A (en) * | 2007-06-06 | 2008-12-10 | 中国农业科学院饲料研究所 | Design and synthesis of novel antimicrobial peptide with high bacteriostatic activity |
| CN101395173A (en) * | 2006-01-16 | 2009-03-25 | 波利弗尔有限公司 | Template-fixed peptidomimetics with antimicrobial activity |
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2013
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1300293A (en) * | 1998-03-16 | 2001-06-20 | 阿斯特拉曾尼卡有限公司 | Process for the preparation of a tetrapeptide |
| CN101395173A (en) * | 2006-01-16 | 2009-03-25 | 波利弗尔有限公司 | Template-fixed peptidomimetics with antimicrobial activity |
| CN101293925A (en) * | 2007-04-29 | 2008-10-29 | 王鹤尧 | Preparation and application of synthetic polypeptide medicaments for treating tubercle bacillus infection contamination |
| CN101319007A (en) * | 2007-06-06 | 2008-12-10 | 中国农业科学院饲料研究所 | Design and synthesis of novel antimicrobial peptide with high bacteriostatic activity |
Non-Patent Citations (1)
| Title |
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| 舒茂等: "基于序列信息的阳离子抗菌肽设计", 《计算机与应用化学》, vol. 29, no. 8, 28 August 2012 (2012-08-28) * |
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