CN110204709A - A kind of cationic antimicrobial cluster high molecular preparation method of peptide for simulating natural antibacterial peptide structure - Google Patents
A kind of cationic antimicrobial cluster high molecular preparation method of peptide for simulating natural antibacterial peptide structure Download PDFInfo
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 125000002091 cationic group Chemical group 0.000 title claims abstract description 5
- 239000003910 polypeptide antibiotic agent Substances 0.000 title claims abstract description 5
- 230000000845 anti-microbial effect Effects 0.000 title claims description 7
- 229920000642 polymer Polymers 0.000 claims abstract description 39
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims description 42
- 239000000243 solution Substances 0.000 claims description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 238000006116 polymerization reaction Methods 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 7
- 125000003368 amide group Chemical group 0.000 claims description 6
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 claims description 6
- 238000007151 ring opening polymerisation reaction Methods 0.000 claims description 6
- 239000008367 deionised water Substances 0.000 claims description 5
- 229910021641 deionized water Inorganic materials 0.000 claims description 5
- 238000004108 freeze drying Methods 0.000 claims description 5
- 239000000376 reactant Substances 0.000 claims description 5
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 claims description 3
- 238000009826 distribution Methods 0.000 claims description 3
- 238000005227 gel permeation chromatography Methods 0.000 claims description 3
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000003115 biocidal effect Effects 0.000 abstract description 13
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 11
- 229920001184 polypeptide Polymers 0.000 abstract description 10
- 230000003013 cytotoxicity Effects 0.000 abstract description 3
- 231100000135 cytotoxicity Toxicity 0.000 abstract description 3
- 239000004599 antimicrobial Substances 0.000 abstract 1
- 238000004088 simulation Methods 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 16
- 229960001269 glycine hydrochloride Drugs 0.000 description 16
- 239000002904 solvent Substances 0.000 description 14
- 238000010189 synthetic method Methods 0.000 description 14
- 239000000126 substance Substances 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 230000035484 reaction time Effects 0.000 description 10
- 241000894006 Bacteria Species 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 9
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N deuterated chloroform Substances [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 230000005311 nuclear magnetism Effects 0.000 description 5
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241000191967 Staphylococcus aureus Species 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 238000007334 copolymerization reaction Methods 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 229920002379 silicone rubber Polymers 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 125000003963 dichloro group Chemical group Cl* 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical class COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 235000010300 dimethyl dicarbonate Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000005588 protonation Effects 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 239000004945 silicone rubber Substances 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 238000000089 atomic force micrograph Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- -1 hydrogen furans Chemical class 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 108010094020 polyglycine Proteins 0.000 description 1
- 229920000232 polyglycine polymer Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/42—Polyamides containing atoms other than carbon, hydrogen, oxygen, and nitrogen
Abstract
The invention discloses a kind of cationic antimicrobials for simulating natural antibacterial peptide structure to cluster the high molecular preparation method of peptide, its main feature is that the structure of simulation natural antibacterial polypeptide, electropositive hydrophilic radical and alkyl chain hydrophobic grouping are introduced into cluster peptide molecule, so that cluster peptide has both the two-fold advantage of antibiotic property and class peptide molecule itself.The present invention realizes the regulation to cluster peptide molecule antibacterial selectivity by adjusting the content of alkyl chain on polymer molecular chain to adjust the antibiotic property and cytotoxicity of polymer.
Description
Technical field
The invention belongs to boiomacromolecules to synthesize field, and in particular to a kind of molecular side chain contains the antibacterial of amido and alkyl
Type random copolymer.
Background technique
Countless life has been saved at the beginning of antibiotic invention.But in recent decades, the continuous abuse of antibiotic causes " super
This unusual stubborn problem of bacterium ".Scientific research personnel continually develops new antibiotic, to delay arriving for " superbacteria " problem
Come, but after all palliative.And natural antibacterial polypeptide had once been considered as that can solve having for " superbacteria " huge for one kind
The high molecular material of big potentiality.When microorganism is invaded, most animal and plant body can all generate some substances to intrusive body
It is resisted, most in these substances is antibacterial polypeptide.In structure, such polypeptide typically contains 10-50 or so amino acid
Composition, last point of amino acid of strand are the hydrophilic section of cationic, and another part is the hydrophobic section containing alkyl chain.It is such
Antibacterial polypeptide has the advantages that immunogenicity is lower, sterilization is rapid, broad-spectrum antiseptic.Bacterium can not only be killed, to it is some virus,
Cancer cell, fungi also have killing effect, while not having any destruction to normal cell.
Cluster peptide is also known as nitrogen and replaces polyglycine, is a kind of macromolecule for having structure similar to polypeptide, it and polypeptide
In structure is not both that the R group being connected on the carbon of center originally is transferred on nitrogen-atoms.In nature, since class peptide does not have center
Carbon and amido bond so that class peptide does not have secondary structure and the not interaction of hydrogen bond, and are not easy to be digested.Class peptide has
Many is different from the excellent physicochemical property of polypeptide, has not only had good biocompatibility and bioactivity but also has had traditional high score
Sub- material good dissolubility and processability are a kind of very promising bioabsorbable polymer materials, are more and more closed
Note.
It is combined with each other both above, the structure of natural antibacterial polypeptide is simulated, by electropositive hydrophilic segment and hydrophobicity
Alkyl segment is introduced into cluster peptide, is obtained the antibiotic property for having both natural antibacterial polypeptide and is clustered a series of macromolecules of peptide advantage
Material.High molecular material great potential on solving the problems, such as " superbacteria ".
The present invention reports a series of cluster peptides prepared with ring-opening polymerisation and/alkynes-mercaptan click chemistry method of modifying
Macromolecule finally makes side group with hydrophobic alkyl chain and electropositive amido and has antibacterial behavior.Cluster the antibacterial of peptide
Property can be by long alkyl chains, alkyl segment in the content of content and amido segment on class peptide molecule chain on class peptide molecule chain
Three principal elements determine.The present invention has studied in detail three major determinants for influencing the cluster peptide antibiotic property, and
Polymer is compared to the antibiotic property of variety classes bacterium and to histiocytic toxicity.Finally to a series of antibacterial effects compared with
Good polymer has carried out mouse animal experiment, characterizes practical antibacterial effect in animal body with this.
Summary of the invention
The purpose of the present invention is synthesize a kind of strand side group to be total to electropositive amido and the random of hydrophobic alkyl chain
Cluster peptide.
1, according to an embodiment of the invention, the compound is polymer shown in formula (I):
Wherein, m value is the number that 40 or so, n value is 10-40.
The present invention is as follows about the synthetic method of antibiotic property cluster peptide:
(1) under room temperature, n-butylamine is added in glyoxalic acid and is reacted, to which hydrochloric acid reflux, imido are added after reaction
Purification is recrystallized after base protonation.Filtration drying obtains N- normal-butyl and replaces glycine hydrochloride.
(2) triethylamine, di-tert-butyl dicarbonate is added in product one step up, BOC by the hydrogen atom on substituted imido,
Purpose is to protect amido.The N- normal-butyl for finally obtaining BOC protection replaces glycine hydrochloride.
(3) phosphorus trichloride cyclization is added in step product upwards, obtains N- normal-butyl-NCA.
(4) n-butylamine in above-mentioned steps is replaced with into n-hexylamine, corresponding molar ratio, reaction condition are constant, can obtain N-
N-hexyl-NCA.
(5) synthetic method of N- propargyl-NCA and N- allyl-NCA are in our prior in patent
(2018103388816 and 2018103392883, have disclosed at present, unauthorized) have been described in detail.
(6) two kinds of NCA feed intake by design proportion, and the Bian amine that corresponding amount is added causes ring-opening polymerisation, and it is poly- to obtain random copolymerization
Class peptide.
(7) photoinitiator (DMPA), mercaptoethylmaine are added in resulting polymers, it is anti-that click chemistry occurs under ultraviolet lighting
It answers, double bond on strand is modified, finally obtain the random copolymerization cluster peptide with antibiotic property.
In above-mentioned synthetic method, step (1) is reacted at room temperature in dichloromethane solvent, and the reaction time is that 3-5 is small
When, concretely 3 hours, 4 hours, 5 hours, methylene chloride was removed after reaction；Step is added just in (1)
Butylamine is 0.5 times of the amount of acetaldehyde acid substance；Required concentration of hydrochloric acid is 2mol/L when reflux in step (1), and hydrochloric acid is added
The amount of substance be 2 times of amount of n-butylamine substance；In step (1) reflux need to 110 DEG C at a temperature of be refluxed overnight, revolving is removed
Remove the solvent and unreacted hydrochloric acid in system.Solid after methanol dissolution revolving is then first added, is slow added into excess
Ether -20 DEG C at a temperature of recrystallization overnight.Final filtration is dry to can be obtained pure N- normal-butyl substitution glycinate
Hydrochlorate.
In above-mentioned synthetic method, N- normal-butyl is first replaced glycine hydrochloride to be dissolved in water by step in (2), is added three
Ethamine provides alkaline environment for reaction, and di-tert-butyl dicarbonate is added and provides blocking group BOC；Two dimethyl dicarbonates in step (2)
Butyl ester, triethylamine, N- normal-butyl replace the amount of the substance of glycine hydrochloride to be added in the ratio of 3.5-4.5:7-8:1；Step
(2) a little heat release of reaction meeting, reacts, the reaction time is 18 hours at room temperature；It reacts and completes to step (2), separatory funnel
It is middle to wash away excessive di-tert-butyl dicarbonate with n-hexane, it is rear that 1mol/L hydrochloric acid is added, system pH is adjusted to 2 or so, mixture
It is extracted with ethyl acetate, adds saturated salt solution and wash away excessive hydrochloric acid, obtained after final drying, revolving removing solvent pure
The N- normal-butyl of net BOC protection replaces glycine hydrochloride.
In above-mentioned synthetic method, step further removes water the product for obtaining upper step in (3)；Reaction is molten in step (3)
Agent is anhydrous methylene chloride, is prevented after cyclization by the hydrone open loop in system；Phosphorus trichloride is added in step (3) as conjunction
Ring catalyst, the amount that substance is added is 2.5 times of reactant；Step (3) needs to react under nitrogen protection, and the reaction time is 3 small
When, reaction temperature is 0 DEG C；Methylene chloride and catalyst phosphorus trichloride is removed in vacuum in step (3) after the reaction was completed, rear to be added
15-20mL anhydrous methylene chloride extracts the NCA in mixture, removes solvent again and anhydrous tetrahydro furan 15mL is added, by four
Hydrogen tetrahydrofuran solution, which pours into, settles purification in 150mL anhydrous n-hexane.NCA need to settle purification three times in step (3).
In above-mentioned synthetic method, step (6) is mixed two kinds of NCA by corresponding proportion, adds the desired amount of initiator Bian
Amine ring-opening polymerisation；Step (6) polymerization reaction carries out in anhydrous tetrahydro furan, and reaction temperature is 50 DEG C, and the reaction time, 24-48 was small
When, concretely 24 hours, 36 hours, 48 hours；After the reaction was completed excessive cold second is added in polymer solution by step (6)
It is settled in ether, polymer is obtained after centrifugal drying.
In above-mentioned synthetic method, polymer in step (7): fragrant breath dimethyl ether (DMPA) of peace: mercaptoethylmaine is according to 100:5:
1000 ratio, which is added in DMF, to be dissolved, and is removed oxygen in reaction flask, is filled with nitrogen protection, and ultraviolet lighting reacts at room temperature, reaction
Time is 4 hours；Step (7) light source is ultraviolet source (wavelength 270nm-400nm)；Step (7) is being gone after the reaction was completed
Freeze-drying obtains final antibacterial cluster peptide after dialysis removes unreacted small molecule in ionized water.
2, according to an embodiment of the invention, the compound is formula (II) compound represented:
Wherein, m value is the number that 40 or so, n value is 10-40.
The present invention is as follows about the synthetic method of antibiotic property cluster peptide:
(1) under room temperature, n-hexylamine is added in glyoxalic acid and is reacted, to which hydrochloric acid reflux, imido are added after reaction
Purification is recrystallized after base protonation.Filtration drying obtains N- n-hexyl and replaces glycine hydrochloride.
(2) triethylamine, di-tert-butyl dicarbonate is added in product one step up, BOC is by the hydrogen atom on substituted imido
Replace.The N- n-hexyl for obtaining BOC protection replaces glycine hydrochloride.
(3) phosphorus trichloride cyclization is added in step product upwards, obtains N- n-hexyl-NCA.
(4) it feeds intake by design proportion for two kinds of N- n-hexyl-NCA and N- allyl-NCA, the Bian amine that corresponding amount is added causes
Ring-opening polymerisation obtains random copolymerization cluster peptide.
(5) photoinitiator, mercaptoethylmaine are added in resulting polymers, click chemistry reaction occurs under ultraviolet lighting, it is right
Double bond is modified on strand, finally obtains the random copolymerization cluster peptide with antibiotic property.
In above-mentioned synthetic method, step (1) is reacted at room temperature in dichloromethane solvent, and the reaction time is that 3-5 is small
When, concretely 3 hours, 4 hours, 5 hours, methylene chloride was removed after reaction；Step is added just in (1)
Hexylamine is 0.5 times of the amount of acetaldehyde acid substance；Required concentration of hydrochloric acid is 2mol/L when reflux in step (1), and hydrochloric acid is added
The amount of substance be 2 times of amount of n-hexylamine substance；In step (1) reflux need to 110 DEG C at a temperature of be refluxed overnight, revolving is removed
Remove the solvent and unreacted hydrochloric acid in system.Solid after methanol dissolution revolving is then first added, is slow added into excess
Tetrahydrofuran -20 DEG C at a temperature of recrystallization overnight.Final filtration is dry to can be obtained the pure sweet ammonia of N- n-hexyl substitution
Acid hydrochloride.
In above-mentioned synthetic method, N- n-hexyl is first replaced glycine hydrochloride to be dissolved in water by step in (2), is added three
Ethamine provides alkaline environment for reaction, and di-tert-butyl dicarbonate is added and provides blocking group BOC；Two dimethyl dicarbonates in step (2)
Butyl ester, triethylamine, N- n-hexyl replace the amount of the substance of glycine hydrochloride to be added in the ratio of 3.5-4.5:7-8:1；Step
(2) a little heat release of reaction meeting, reacts, the reaction time is 18 hours at room temperature；It reacts and completes to step (2), separatory funnel
It is middle to wash away excessive di-tert-butyl dicarbonate with n-hexane, it is rear that 1mol/L hydrochloric acid is added, system pH is adjusted to 2 or so, mixture
It is extracted with ethyl acetate, adds saturated salt solution and wash away excessive hydrochloric acid, obtained after final drying, revolving removing solvent pure
The N- n-hexyl of net BOC protection replaces glycine hydrochloride.
In above-mentioned synthetic method, step further removes water the product for obtaining upper step in (3)；Reaction is molten in step (3)
Agent is anhydrous methylene chloride, is prevented after cyclization by the hydrone open loop in system；Phosphorus trichloride is added in step (3) as conjunction
Ring catalyst, the amount that substance is added is 2.5 times of reactant；Step (3) needs to react under nitrogen protection, and the reaction time is 3 small
When, reaction temperature is 0 DEG C；Methylene chloride and catalyst phosphorus trichloride is removed in vacuum in step (3) after the reaction was completed, rear to be added
15-20mL anhydrous methylene chloride extracts the NCA in mixture, removes solvent again and anhydrous tetrahydro furan 15mL is added, by four
Hydrogen tetrahydrofuran solution, which pours into, settles purification in 150mL anhydrous n-hexane.NCA need to settle purification three times in step (3).
In above-mentioned synthetic method, step (4) is mixed two kinds of NCA by corresponding proportion, adds the desired amount of initiator Bian
Amine ring-opening polymerisation；Step (4) polymerization reaction carries out in anhydrous tetrahydro furan, and reaction temperature is 50 DEG C, and the reaction time, 24-48 was small
When, concretely 24 hours, 36 hours, 48 hours；After the reaction was completed excessive cold second is added in polymer solution by step (4)
It is settled in ether, polymer is obtained after centrifugal drying.
In above-mentioned synthetic method, polymer in step (5): fragrant breath dimethyl ether (DMPA) of peace: mercaptoethylmaine is according to 100:5:
500 ratio, which is added in DMF, to be dissolved, and is removed oxygen in reaction flask, is filled with nitrogen protection, and ultraviolet lighting reacts at room temperature, reaction
Time is 4 hours；Step (5) light source is ultraviolet source (wavelength 270nm-400nm)；Step (5) is being gone after the reaction was completed
Dialysis removes unreacted small molecule in ionized water, and rear freeze-drying obtains final antibacterial cluster peptide.
Chemicals used in each reaction, reagent remove specified otherwise and purchase in commercial sources in the present invention, this
The text synthetic method has at low cost, easy to operate, the features such as equipment is simple, and raw material is easy to get.Synthesize obtained antimicrobial form
Peptide high molecular material is clustered, antibiotic property can be regulated and controled by the degree of polymerization, hydrophilic segment/hydrophobic segment ratio, long alkyl chains.This hair
The high molecular material of bright offer can be applied to the fields such as biological medicine, intellectual material, have a extensive future, and have solution " super thin
The very high potential of bacterium " problem.
Detailed description of the invention
Fig. 1 is NBG-NCA1H NMR spectra.
Fig. 2 is NHG-NCA1H NMR spectra.
Fig. 3 is the synthesis of NAG-NCA1H NMR spectra.
Fig. 4 is PNAG40-r-PNHG40Cluster peptide1H NMR spectra.
Fig. 5 is PNAGm-r-PNHGnUnder various concentration, the survival rate of staphylococcus aureus.
Fig. 6 is PNAGm-r-PNHGnUnder various concentration, the survival rate of Escherichia coli.
Fig. 7 is PNAGm-r-PNHGnUnder various concentration, the survival rate of Pseudomonas aeruginosa.
Fig. 8 is PNAGm-r-PNHGnHemolysis rate under various concentration.
Fig. 9 is PNAGm-r-PNHGnChange of size figure under various concentration.
Figure 10 is polymer respectively in the AFM and TEM image of 2000mg/L, 20mg/L.
Figure 11 is the histotomy after mouse culture.
Figure 12 is that the silicone rubber plate after mouse culture counts figure through the bacterium colony of solid medium culture.
Specific embodiment
The present invention is further illustrated by embodiment, but the present invention is not limited thereto.The embodiment of the present invention can make this
The present invention is more completely understood in technical professional.
Experimental method used in following embodiments is conventional method unless otherwise specified.NCA purity passes through nuclear-magnetism
Hydrogen spectrum measurement, Bruker 500MHz, CDCl3For solvent, polymer number-average molecular weight is measured by gel permeation chromatography, SSI
Pump connected to Wyatt Optilab DSP, DMF are solvent, flow velocity 1mL min-1, 50 DEG C of test temperature.
The preparation of cluster peptide shown in embodiment 1, formula (III)
(1) 60g (0.4mol, aqueous solution) glyoxalic acid and 300mL methylene chloride are added in 500mL round-bottomed flask, then to
It is slowly added to 19.7mL (0.2mol) n-butylamine in flask, reacts 4 hours at room temperature.Revolving removes solvent dichloro after the reaction was completed
Methane is added 110 DEG C of 2M HCl aqueous solution and flows back 18 hours.After revolving removes aqueous solvent and excessive HCl, 30mL is added
Methanol dissolution, is then slowly added into 300 mL ether, is put into -20 DEG C of refrigerator and recrystallizes overnight.Final filtration is dried to obtain N-
Normal-butyl replaces glycine hydrochloride.
(2) glycine hydrochloride is replaced to be dissolved in 200mL deionized water 16.6g (0.1mol) N- normal-butyl, successively
76.3g (0.35 mol) di-tert-butyl dicarbonate, 97mL (0.7mol) triethylamine is added, reacts 18 hours at room temperature.Wait react
The excessive di-tert-butyl dicarbonate of system first is washed away with 3*100mL n-hexane after the completion, 1M hydrochloric acid is added by pH value and is adjusted to 2 left sides
It is right.Then 3*100mL ethyl acetate is added and extracts product, extract liquor is added saturated sodium chloride solution and washes away excessive hydrochloric acid, passes through
Magnesium sulfate is dry, revolving removes solvent, and the N- normal-butyl for finally obtaining BOC protection replaces glycine hydrochloride.
(3) the upper step product of 10.7g (0.047mol) is added in 500mL Shrek bottle and further vacuumizes water removal, with
The dissolution of 300mL anhydrous methylene chloride is added afterwards, under conditions of being stirred continuously in 0 DEG C of ice-water bath, 10mL tri- is added dropwise into system
Phosphorus chloride.Methylene chloride and catalyst phosphorus trichloride is removed in vacuo after 4 hours in reaction, continuously adds the anhydrous dichloro of 15mL
Methane, after dichloromethane solution be slowly added to be placed into -20 DEG C of refrigerators in 150 mL anhydrous n-hexanes recrystallize.In repetition
It states recrystallization process three times, finally obtains pure N- normal-butyl-NCA.Nucleus magnetic hydrogen spectrum1H NMR(500MHz,CDCl3)δ:4.08
(s, 2H), 3.24 (t, 2H), 1.61 (m, 2H), 1.22 (m, 2H), 0.85 (t, 3H) nuclear-magnetism figure are shown in Figure of description 1c.
(4) 278mg (2mmol) N- propargyl-NCA, 314mg (2mmol) N- normal-butyl-NCA are dissolved in the anhydrous tetrahydro of 6mL
In furans, then preheated in 50 DEG C of oil bath.Bian amine is dissolved in the solution that 2%-3% is made into anhydrous tetrahydro furan, to
It is added in reactant 252 μ L (0.05 mmol, the Bian amine aqueous solution of 2.38% mass fraction), reaction is reacted 48 hours at 50 DEG C.
Polymer solution is poured into cold n-hexane and settled after the reaction was completed, 287mg white powder is obtained after centrifugal drying.Gel seeps
Saturating chromatography measures number-average molecular weight 9300g/L, molecular weight distribution 1.43, number-average degree of polymerization 36:35.
(5) 100mg polymer powder is added in reaction flask together with DMPA, 1000mg mercaptoethylamine hydrochloride of 5mg,
2mL DMF is added, is reacted 4 hours under nitrogen atmosphere, 270nm ultraviolet lamp.Mixture solution is placed in retention after the reaction was completed
Molecular weight is that the bag filter of 1000Da is dialysed three days in deionized water.Freeze-drying later obtains (93mg) antimicrobial form cluster peptide.
The preparation of cluster peptide shown in embodiment 2, formula (IV)
(1) 60g (0.4mol, aqueous solution) glyoxalic acid and 300mL methylene chloride are added in 500mL round-bottomed flask, then to
It is slowly added to 26mL (0.2mol) n-hexylamine in flask, reacts 4 hours at room temperature.Revolving removes solvent dichloromethane after the reaction was completed
Alkane is added 110 DEG C of 2M HCl aqueous solution and flows back 18 hours.After revolving removes aqueous solvent and excessive HCl, 30mL first is added
Alcohol dissolution, is then slowly added into 300 mL tetrahydrofurans, is put into -20 DEG C of refrigerator and recrystallizes overnight.Final filtration is dried to obtain
N- n-hexyl replaces glycine hydrochloride.
(2) glycine hydrochloride is replaced to be dissolved in 200mL deionized water 20.5g (0.1mol) N- n-hexyl, successively
76.3g (0.35 mol) di-tert-butyl dicarbonate, 97mL (0.7mol) triethylamine is added, reacts 18 hours at room temperature.Wait react
The excessive di-tert-butyl dicarbonate of system first is washed away with 3*100mL n-hexane after the completion, 1M hydrochloric acid is added by pH value and is adjusted to 2 left sides
It is right.Then 3*100mL ethyl acetate is added and extracts product, extract liquor is added saturated sodium chloride solution and washes away excessive hydrochloric acid, passes through
Magnesium sulfate is dry, revolving removes solvent, and the N- n-hexyl for finally obtaining BOC protection replaces glycine hydrochloride.
(3) the upper step product of 12.4g (0.046mol) is added in 500mL Shrek bottle and further vacuumizes water removal, with
The dissolution of 300mL anhydrous methylene chloride is added afterwards, under conditions of being stirred continuously in 0 DEG C of ice-water bath, 10mL tri- is added dropwise into system
Chloromethanes.Methylene chloride and catalyst phosphorus trichloride is removed in vacuo after 4 hours in reaction, continuously adds the anhydrous dichloro of 15mL
Methane, after dichloromethane solution is slowly added to settle in the anhydrous n-hexane that 150 mL are stirred continuously, remove NCA in it is miscellaneous
Matter repeats above-mentioned infall process three times, finally obtains pure N- n-hexyl-NCA.Nucleus magnetic hydrogen spectrum1H NMR(500MHz,
CDCl3) (t, 3H) nuclear-magnetism figure of δ: 4.12 (s, 2H), 3.31 (t, 2H), 1.67 (m, 2H), 1.38 (m, 3*2H), 0.92 is shown in
Bright book attached drawing 2c.
(4) 282mg (2mmol) N- allyl-NCA, 370mg (2mmol) N- n-hexyl-NCA are dissolved in 6.5mL anhydrous four
In hydrogen furans, then preheated in 50 DEG C of oil bath.Bian amine is dissolved in the solution that 2%-3% is made into anhydrous tetrahydro furan,
It is added into reactant 252 μ L (0.05mmol, the Bian amine aqueous solution of 2.38% mass fraction), reaction reaction 48 at 50 DEG C is small
When.Polymer solution is poured into cold ether and settled after the reaction was completed, 312mg white powder is obtained after centrifugal drying.Nuclear-magnetism
Hydrogen spectrum1H NMR (500MHz): 3.7-4.3 (bm, 4H), 5.2 (s, 1H), 5.5-6.0 (d, 2H) gel permeation chromatography measure number
Average molecular weight 4500g/L, molecular weight distribution 1.29, number-average degree of polymerization 47:43.Nuclear-magnetism figure is shown in instruction sheet 4.
(5) 100mg polymer powder is added in reaction flask together with DMPA, 500mg mercaptoethylamine hydrochloride of 5mg,
2mL DMF is added, is reacted 4 hours under nitrogen atmosphere, 270nm ultraviolet lamp.Mixture solution is placed in retention after the reaction was completed
Molecular weight is that the bag filter of 1000Da is dialysed three days in deionized water.Freeze-drying later obtains (82mg) antimicrobial form cluster peptide.
The bacterium characterization of cluster peptide shown in embodiment 1,2:
Bacterium freeze-dried powder (staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa) addition fresh culture is incubated overnight,
With the OD value after fresh culture dilution bacterial suspension in 600nm wavelength measurement bacterial solution, mark when OD value is 0.07 or so
Fa Lanshi turbidity standard is 108CFU/mL continues 1000 times of dilution on the basis of this concentration, obtains 105The bacterium of CFU/mL
Solution uses to test.
Polymer formulation is the aqueous solution of 20mg/mL, takes 40 μ L polymer solutions to be added (each in the 11st column of 96 orifice plates
4 groups of parallel controls of sample, 2 samples of an orifice plate), take 160 μ L fresh culture be added the 11st column in, 100 μ L it is fresh
Culture medium is added in 1-10 column, carries out serial dilution operation and (takes 100 μ L of solution in the 11st column hole with the volley of rifle fire, the 10th column are added
It is uniformly mixed in hole, takes 100 μ L of solution in the 10th column hole with the volley of rifle fire, be added in the 9th column hole and be uniformly mixed ..., use the volley of rifle fire
100 μ L of solution in the 3rd column hole is taken, is added in the 2nd column hole and is uniformly mixed, takes 100 μ L of solution in the 2nd column hole to throw aside with the volley of rifle fire), it is dilute
With the volley of rifle fire, into 96 orifice plates, 100 μ L 10 are added in all holes after the completion of releasing5The bacterial solution of CFU/mL is added into the 12nd column
100 μ L bactericidal liquids.Positive control is classified as so that the 1st be classified as negative control in orifice plate, the 12nd, and polymer solution concentration is from the 11st column
It is diluted at double to the 2nd column.
After being cultivated 18 hours in 37 DEG C of orifice plate merging, 120 revs/min of shaking table, its OD value is measured in 600nm, handles number
It is presented according to chart mode.See Figure of description 5,6,7, is the polymer of embodiment 2 respectively to staphylococcus aureus, large intestine
The survival rate of bacterium after bacillus, Pseudomonas aeruginosa effect, it is seen that polymer just has sterilization effect well at very low concentrations
Fruit is even more especially just to have 100% killing effect in 32 μ g/mL to staphylococcus aureus.By the polymerization of embodiment 2
The method of object application serial dilution is placed in orifice plate with screech owl rabbit erythrocyte cultivates, and orifice plate OD value is tested under the wavelength of 572nm,
Equally data are presented with chart.See Figure of description 8, is just shown known in figure when polymer concentration is lower bigger
Cytotoxicity, in other words, under same concentration, toxicity of the polymer to the toxicity of cell as bactericidal effect or even to cell
It is bigger.Cytotoxicity can be seen in the concentration for continuing growing polymer to be significantly reduced again.To under polymer various concentration
Solution testing DLS, see Figure of description 9, it can be seen that clustering phenomena has occurred in polymer in higher concentrations, so that polymer
Toxicity decline for cell.Pattern of the sample under various concentration further is characterized with AFM, TEM, sees Figure of description
10。
Polymer coating film is finally taken into 10 μ L 10 in diameter 0.5cm silicone rubber plate8CFU/mL bacterial suspension is seeded in silicon
On sheet rubber, it is subcutaneous to be placed in back of mice, and mouse is dissected and is sliced after 5 days, sees Figure of description 11, it is seen that is coated with polymerization
The slice inflammatory cell of object side is almost invisible, and the inflammatory reaction of reference side is more serious.Silicon rubber after mouse culture
Piece taking-up is counted with solid medium culture, sees Figure of description 12, it is seen that reference clump count, which is significantly more than, is coated with polymer
The silicon rubber of side.
Claims (6)
1. a kind of cationic antimicrobial for simulating natural antibacterial peptide structure clusters the high molecular preparation method of peptide.
2. according to claim 1, the characteristics of preparation method is the means modified by ring-opening polymerisation and click chemistry
The cluster peptide with antibacterial properties is synthesized, the polymer such as structural formula I and formula II:
3. according to claim 2, the characteristics of polymer is that side group contains hydrophilic amido segment and hydrophobic alkyl
Segment.
4. according to claim 2, the polymer, it is characterised in that the number of m 40, n 10,20,40 or so.
5. according to claim 3, the polymer the preparation method is as follows:
100mg polymer powder is added in reaction flask together with DMPA, 1000mg mercaptoethylamine hydrochloride of 5mg, 2mL is added
DMF reacts 4 hours under nitrogen atmosphere, 270nm ultraviolet lamp.Mixture solution, which is placed in molecular cut off, after the reaction was completed is
The bag filter of 1000Da is dialysed three days in deionized water.Freeze-drying later obtains (93mg) antimicrobial form cluster peptide.
6. the method for producing polymer of the degree of polymerization m=40, n=40 are as follows according to claim 4:
278mg (2mmol) N- propargyl-NCA, 314mg (2mmol) N- normal-butyl-NCA are dissolved in 6mL anhydrous tetrahydro furan,
Then it is preheated in 50 DEG C of oil bath.Bian amine is dissolved in the solution that 2%-3% is made into anhydrous tetrahydro furan, into reactant
It is added 252 μ L (0.05mmol, the Bian amine aqueous solution of 2.38% mass fraction), reaction is reacted 48 hours at 50 DEG C.Reaction is completed
Polymer solution is poured into cold n-hexane and settled afterwards, 287mg white powder is obtained after centrifugal drying.Gel permeation chromatography is surveyed
Number average molecular weight 9300g/L, molecular weight distribution 1.43, number-average degree of polymerization 36:35.
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| WO2020228758A1 (en) * | 2019-05-14 | 2020-11-19 | 青岛科技大学 | Method for preparing cationic antimicrobial polypeptoid polymer simulating natural antimicrobial peptide structure |
| CN113476614A (en) * | 2021-07-07 | 2021-10-08 | 青岛科技大学 | Uniform polyelectrolyte composite vesicle and preparation method thereof, antibacterial vesicle, hydrophobic substance-encapsulated vesicle and anti-adhesion vesicle |
| CN113583236A (en) * | 2021-07-22 | 2021-11-02 | 江苏大学 | Preparation method of amphiphilic carbohydrate-containing polypeptide simulating natural antifreeze protein structure |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100222255A1 (en) * | 2009-02-24 | 2010-09-02 | Kent Kirshenbaum | Peptoid oligomers, pharmaceutical compositions and methods of using the same |
| CN106117548A (en) * | 2016-06-27 | 2016-11-16 | 中国科学院长春应用化学研究所 | A kind of amino acidic group cluster peptide and preparation method thereof |
| WO2017209805A1 (en) * | 2016-06-01 | 2017-12-07 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Hydrophobically modified polypeptoids and uses thereof |
Family Cites Families (4)
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| CN107880263B (en) * | 2017-11-06 | 2021-07-02 | 青岛科技大学 | Temperature-responsive clustering peptide with side chain containing oligo-polyethylene glycol and preparation method thereof |
| CN108484905A (en) * | 2018-04-16 | 2018-09-04 | 青岛科技大学 | A kind of side chain has the cluster peptide and preparation method thereof of UCST behaviors containing carboxyl |
| CN110204709A (en) * | 2019-05-14 | 2019-09-06 | 青岛科技大学 | A kind of cationic antimicrobial cluster high molecular preparation method of peptide for simulating natural antibacterial peptide structure |
-
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100222255A1 (en) * | 2009-02-24 | 2010-09-02 | Kent Kirshenbaum | Peptoid oligomers, pharmaceutical compositions and methods of using the same |
| WO2017209805A1 (en) * | 2016-06-01 | 2017-12-07 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Hydrophobically modified polypeptoids and uses thereof |
| CN106117548A (en) * | 2016-06-27 | 2016-11-16 | 中国科学院长春应用化学研究所 | A kind of amino acidic group cluster peptide and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| CHAO XING ET AL.: "Charge-Determined LCST/UCST Behavior in Ionic Polypeptoids", 《BIOMACROMOLECULES》 * |
| JIYOUN LEE ET AL.: "Effect of side chain hydrophobicity and cationic charge on antimicrobial activity and cytotoxicity of helical peptoids", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020228758A1 (en) * | 2019-05-14 | 2020-11-19 | 青岛科技大学 | Method for preparing cationic antimicrobial polypeptoid polymer simulating natural antimicrobial peptide structure |
| CN113476614A (en) * | 2021-07-07 | 2021-10-08 | 青岛科技大学 | Uniform polyelectrolyte composite vesicle and preparation method thereof, antibacterial vesicle, hydrophobic substance-encapsulated vesicle and anti-adhesion vesicle |
| CN113476614B (en) * | 2021-07-07 | 2023-08-25 | 青岛科技大学 | Homopolymeric electrolyte composite vesicle, preparation method thereof, antibacterial vesicle, vesicle coated with hydrophobic substance and anti-adhesion vesicle |
| CN113583236A (en) * | 2021-07-22 | 2021-11-02 | 江苏大学 | Preparation method of amphiphilic carbohydrate-containing polypeptide simulating natural antifreeze protein structure |
| CN113583236B (en) * | 2021-07-22 | 2022-07-22 | 江苏大学 | Preparation method of amphiphilic carbohydrate-containing polypeptide simulating natural antifreeze protein structure |
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