CN110003308A - A kind of small molecule toxins isolated and purified from the thick poison of Araneus ventricosus and application - Google Patents
A kind of small molecule toxins isolated and purified from the thick poison of Araneus ventricosus and application Download PDFInfo
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- CN110003308A CN110003308A CN201910299466.9A CN201910299466A CN110003308A CN 110003308 A CN110003308 A CN 110003308A CN 201910299466 A CN201910299466 A CN 201910299466A CN 110003308 A CN110003308 A CN 110003308A
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
- A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
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- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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Abstract
The invention belongs to technical field of chemistry and chemical engineering, it is related to a kind of small molecule toxins isolated and purified from the thick poison of Araneus ventricosus and application, the small molecule toxins isolated and purified from the thick poison of Araneus ventricosus are quaternary amines small molecule toxins, relative molecular weight is 757.5112, and the molecular formula for the small molecule toxins that NMR structure parsing is isolated and purified from the thick poison of Araneus ventricosus is C36H64O5N13, the present invention provides it is a kind of there is selective active on insect, influenced that smaller, effect is stronger by pH and effect it is more stable from Araneus ventricosus it is thick it is malicious in the small molecule toxins that isolate and purify and application.
Description
Technical field
The invention belongs to technical field of chemistry and chemical engineering, it is related to a kind of small molecule toxins and application, more particularly to a kind of from big
The small molecule toxins isolated and purified in the thick poison of abdomen epeira and application.
Background technique
Araneus ventricosus (Araneus ventricosus) be it is a kind of with insect be food medium-sized spider, be subordinate in classification
In Arthropoda, Arachnoidea, Araneida, Yuan Zhu section, Aranea.Between spot bandit spider be at present be distributed in the world most wide spider it
One, existing in venom can largely anaesthetize or the toxic component of lethal insect.Explore these separated from the thick poison of Araneus ventricosus it is pure
The structure and functional characteristics of the small molecule toxins of change, neurobiological study tool reagent and drug may be used as by being screened out from it
And the precursor molecule of insecticide.Currently, the research for Araneus ventricosus venom is seldom, Japanese Kawai et al. has found Araneus ventricosus
Malicious sac extract can inhibit lobster nerve neuromuscular junction excitatory postsynaptic potential (EPSP), not influence on inhibitory postsynaptic potential；
Furthermore the poison sac extract can inhibit the postsynaptic membrane of glutamate induction to depolarize, and to the cynapse rear mold of asparatate induction
Depolarising does not influence.Other have no the research report about the spider toxin.
So far, a kind of non-protein small molecule toxins are had found in the venom of spider and wasp, through structure solution
Analysis, belongs to acetyl polyamines micromolecular, their majorities act on the glutamate receptor of invertebrate and vertebrate, non-valley ammonia
Acid acceptor or acetylcholinergic receptor, these molecules to the inhibition concentration of receptor in 0.01 μm of ol/L to 100 μm of ol/L range, no
Difference is obvious between same molecule.Meanwhile having no these acetyl polyamines micromoleculars to the selective work of insect sodium-ion channel
Report.
Summary of the invention
In order to solve the above technical problems in background technology, the present invention provides a kind of pair of insects to have selectivity
Activity is influenced smaller, the more stable small molecule poison isolated and purified from the thick poison of Araneus ventricosus of the stronger and effect of effect by pH
Element and application.
To achieve the goals above, the present invention adopts the following technical scheme:
A kind of small molecule toxins isolated and purified from the thick poison of Araneus ventricosus, it is described to be isolated and purified from the thick poison of Araneus ventricosus
Small molecule toxins be quaternary amines small molecule toxins.
Preferably, the average molecular of the small molecule toxins provided by the present invention isolated and purified from the thick poison of Araneus ventricosus
Amount is 757.5112, and the molecular formula for the small molecule toxins that NMR structure parsing is isolated and purified from the thick poison of Araneus ventricosus is
C36H64O5N13。
Preferably, the structural formula of the small molecule toxins provided by the present invention isolated and purified from the thick poison of Araneus ventricosus
Are as follows:
The small molecule toxins isolated and purified from the thick poison of Araneus ventricosus as previously described are in insecticide or in Neurobiology
Application in reagent and/or drug.
The small molecule toxins isolated and purified from the thick poison of Araneus ventricosus as described above are to block or block insect sodium completely
The application when mode of ion channel is as insecticide.
It is described from big when the small molecule toxins isolated and purified from the thick poison of Araneus ventricosus block insect sodium-ion channel completely
The use concentration of the small molecule toxins isolated and purified in the thick poison of abdomen epeira is no more than 10 μm of ol/L；It is described from the thick poison of Araneus ventricosus
The small molecule toxins isolated and purified are not more than 1 μm of ol/L to the medium effective concentration of insect sodium-ion channel；It is thick from Araneus ventricosus
The small molecule toxins isolated and purified in poison are 0.77 ± 0.05 μm of ol/L to the medium effective concentration of insect sodium-ion channel.
The invention has the advantages that
The present invention provides a kind of small molecule toxins isolated and purified from the thick poison of Araneus ventricosus and applications, should be from the garden great Fu
The small molecule toxins isolated and purified in the thick poison of spider are quaternary amines small molecule toxins, and relative molecular weight is 757.5112, and nuclear-magnetism is total
The molecular formula for the small molecule toxins that vibration structure elucidation is isolated and purified from the thick poison of Araneus ventricosus is C36H64O5N13.It should be from the garden great Fu
The small molecule toxins isolated and purified in the thick poison of spider with it has been found that more amine molecules have significantly different, and have to insect selective
Activity, the research and development of neurobiological study tool reagent and drug and insecticide in terms of there is certain application before
Scape.Small molecule toxins AVTX-757 energy low dosage quick-anaesthesia insect according to the present invention, but its mechanism is reversible
, more irreversible strong lethal protein micromolecular toxin (such as latrotoxin latroinsectotoxin)
For, lethal dose does not have apparent advantage.Small molecule toxins AVTX-757 of the present invention is selected with stronger insect
Selecting property toxicity is lower than 1 μm of ol/L to the medium effective concentration of insect sodium channel.In structure be quaternary amines molecule, by pH influenced compared with
Small, effect is stronger, more stable.Separating and purifying technology of the present invention has been subjected to many experiments use, it was demonstrated that feasible；It is purified into
AVTX-757 structure and properties analysis repeated with the technologies such as modern biochemistry and electrophysiology, as a result reliably.
The small molecule toxins have toxicity to insect, and to rat and mouse without overt toxicity；It can inhibit blattaria DUM neuron membrane
On voltage-sensitive sodium Channel Current, neurobiological study tool reagent research and development and insecticide in terms of
With certain application prospect.
Detailed description of the invention
Fig. 1 is the structural formula from the Argiopidae polyamines toxin belonged to；
Fig. 2 is the structural formula of Agelenopsis category and the polyamines toxin of wasp Philanthus triangulum；
Fig. 3 is the ion-exchange chromatography peak figure of small molecule toxins AVTX-757 provided by the present invention；
Fig. 4 is the reversed-phase high performance liquid chromatography figure of small molecule toxins AVTX-757 provided by the present invention；
Fig. 5 is the mass spectrogram of small molecule toxins AVTX-757 provided by the present invention；
Fig. 6 is the hydrogen nuclear magnetic resonance spectrogram of small molecule toxins AVTX-757 provided by the present invention；
Fig. 7 is the carbon-13 nmr spectra figure of small molecule toxins AVTX-757 provided by the present invention；
Fig. 8 is the nuclear magnetic resonance DEPT spectrogram of small molecule toxins AVTX-757 provided by the present invention；
Fig. 9 is the nuclear magnetic resonance hsqc spectrum figure of small molecule toxins AVTX-757 provided by the present invention；
Figure 10 is the H1-H1 coupling pattern of small molecule toxins AVTX-757 provided by the present invention；
Figure 11 is the nuclear magnetic resonance HMBC spectrogram of small molecule toxins AVTX-757 provided by the present invention；
Figure 12 is the molecular structural formula figure of small molecule toxins AVTX-757 provided by the present invention；
Figure 13 is blocking effect figure of the small molecule toxins AVTX-757 provided by the present invention to blattaria sodium-ion channel；
Figure 14 is influence diagram of the small molecule toxins AVTX-757 provided by the present invention to rat DRG sodium-ion channel.
Specific embodiment
The present invention provides a kind of small molecule toxins isolated and purified from the thick poison of Araneus ventricosus, should be slightly malicious from Araneus ventricosus
In the small molecule toxins that isolate and purify be the quaternary amines small molecule toxins isolated and purified from the thick poison of Araneus ventricosus, opposite point
Son amount is 757.5112, and the molecular formula for the small molecule toxins that NMR structure parsing is isolated and purified from the thick poison of Araneus ventricosus is
C36H64O5N13, structural formula are as follows:
The small molecule toxins provided by the present invention isolated and purified from the thick poison of Araneus ventricosus are in insecticide or in nerve life
Application in object reagent and/or drug, especially to block or completely in a manner of blocking insect sodium-ion channel as desinsection
Application when agent.When the small molecule toxins isolated and purified from the thick poison of Araneus ventricosus block insect sodium-ion channel completely, from
The use concentration of the small molecule toxins isolated and purified in the thick poison of Araneus ventricosus is no more than 10 μm of ol/L；Divide from the thick poison of Araneus ventricosus
Small molecule toxins from purifying are not more than 1 μm of ol/L to the medium effective concentration of insect sodium-ion channel；It is slightly malicious from Araneus ventricosus
In the small molecule toxins that isolate and purify be 0.77 ± 0.05 μm of ol/L to the medium effective concentration of insect sodium-ion channel.
The present invention has carried out systematic research to the non-protein small molecule toxins in Araneus ventricosus venom, establishes point
From the method for being purified into single non-protein small molecule toxins.And patch clamp technique and living animal toxicity test are utilized, mirror
Toxicity of such fixed small molecule toxins to insect and vertebrate.Micromolecular poison is determined using mass spectrum and nuclear magnetic resonance technique
The molecular formula of element, structural formula and space structure.The molecular structure of AVTX-757 toxin is parsed.By database and document tune
It researches and develops now, most of others non-protein micromolecular toxin are acyl polyamines toxoid, are had from Argiopidae category
ArgTX-636, ArgTX-659, JSTX-3 and NSTX-3 (structural formula is as shown in Figure 1), the AG505 belonged to from Agelenopsis,
The PHTX-433 of AG489, AG468, AG452 and wasp Philanthus triangulum (structural formula is as shown in Figure 2).It should
Toxoid mainly has inhibitory activity to the receptor of mammal.
The preparation method of the small molecule toxins provided by the present invention isolated and purified from the thick poison of Araneus ventricosus is will to acquire
The Araneus ventricosus arrived is slightly malicious, after the ultrafiltration membrane ultrafiltration of 3KDa, collects small molecule sample segment；Then handed over using strong cation
It changes column to separate small molecule sample segment, obtains the ion-exchange chromatography peak containing insect specificity small molecule toxins, then
It selects the target peak detected through biological mass spectrometry to carry out reverse phase-high performance liquid chromatography, obtains pure lps molecule monomer,
Specifically:
1) purifying of AVTX-757
Ion-exchange chromatography is carried out to the small molecule part after Araneus ventricosus slightly malicious ultrafiltration, obtain containing AVTX-757 from
Sub- exchange chromatography peak (Fig. 3).Chromatographic condition: the C18 reversed-phase column of scientific and technological (Shanghai) limited liability company of the moon rising sunXB-
SCX (10mm × 250mm) eluent A is pH6.25,20mM phosphate buffer；Eluent B is the sodium chloride containing 1.25mol/L
PH6.25,20mM phosphate buffer.Linear gradient elution, flow velocity 2.0mL/min, 280nm detection.* standard in Fig. 3 at
Divide after being collected and is freeze-dried to get the component containing AVTX-757.
2) reverse phase-high performance liquid chromatography: the C18 reversed-phase column of scientific and technological (Shanghai) limited liability company of the moon rising sun is utilized
XB-C18 (10 × 250mm) carries out the desalination of sample and further isolates and purifies.Eluent A is containing 2% acetonitrile and 0.1% trifluoro
The deionized water of acetic acid；Eluent B is the trifluoroacetic acid aqueous solution containing 2% deionized water and 0.1% trifluoroacetic acid.Linear gradient is washed
It is de-, flow velocity 2.0mL/min, 280nm detection.Freeze-drying is after the ingredient of * standard in Fig. 4 is collected to get isolating and purifying
Small molecule toxins AVTX-757.
After the small molecule toxins isolated and purified in the thick poison of slave Araneus ventricosus mentioned by the present invention are prepared, it is carried out
Purity and Structural Identification, specifically:
1) mass spectral analysis of the AVTX-757 after separating
Utilize the molecular weight of MALDI-TOF measurement purified toxins albumen.As shown in figure 5,1 positive charge of AVTX-757 band,
It is 757.5112 according to the molecular weight that charge number and charge-mass ratio can calculate the small molecule toxins.Simultaneously as can be seen that purifying
AVTX-757 impurity content afterwards is extremely low, is high sterling.
2) nuclear magnetic resonance spectroscopy and structure elucidation of AVTX-757
1. AVTX-757 hydrogen spectrum and carbon spectrum analysis: using carried out in Brooker VNS-600 Nuclear Magnetic Resonance hydrogen spectrum and
Carbon spectrum analysis (result refers to Fig. 6 and Fig. 7).500 and 600MHz is used to carry out 1H NMR analysis, and 125 and 150MHz is used to
Carry out 13C NMR analysis.Chemical shift (δ) unit is ppm, and coupling constant unit is hertz (Hz).
2. ID NMR speetna acquisition and spectrum analysis: all two-dimentional spectrograms use time phase under phase sensitive mode
The quasi- pulse sorting of incremental method mark-on is acquired with bad method is mutually followed.Solvent isolation is obtained using pre-saturated method.Two-dimensional nucleus
Magnetic resonance spectrum records at room temperature, including COSY spectrum, using the incorporation time of 37 and 73ms, the record data point of COSY be t1 and
T2 is 512 and 2048.It is operated and is observed using software XWINNMR (Bruker) progress.All data are gone to produce by zero padding
Before the COSY. Fourier transform of the raw practical matrix of 2k and 4k, using the sine wave mutually to drift about or sinusoidal popin with one 1/2
Square window function.
According to HRESIMS m/z 758.5129 [M]+Calcd for 758.5129, C36H64O5N13Determine the chemical combination materialization
Formula is: C36H64O5N13,13C-NMR (Fig. 7) and DEPT (Fig. 8) spectrum shows 33 carbon signals, including 3 methyl carbon signals
(δC40.2,40.2,20.4), 14 mesomethylene carbon (δC56.5,55.1,54.6,41.7,41.7,37.5,36.6,31.4,
29.7,25.5,25.5,25.5,25.4,22.2), 9 methine carbon (δC125.1,122.5,119.9,119.9,112.4,
73.3,67.9,60.1,54.1), 7 quaternary carbon (δC177.3,173.7,170.5,158.7,137.8,129.2,111.3), lead to
It crosses1H-NMR (Fig. 6),13C-NMR (Fig. 7), DEPT (Fig. 8),1H-1H COSY (Figure 10), HMBC (Figure 11) and HSQC (Fig. 9) wave spectrum
Data belong to all H and C.(note: 119.9 be 2 carbon, and 41.7 be 2 carbon, and 40.2 be 2 carbon, 25.5-25.4
It is 4 carbon).
1There are the signals 7.64,7.03,7.12,7.37 and 7.23ppm of one group of indolyl radical in H-NMR spectrum, and
In HMBC spectrum, H-3 (δ 7.64) and C-1 (δ 111.3), C-2 (δ 129.2), C-5 (δ 122.5), C-6 (δ 112.4), C-7 (δ
137.8) there are coherent signal, determine that the compound contains an indolyl radical, the H-11 (δ 4.49) and C-1 (δ in HMBC spectrum
111.3), C-10 (δ 31.4), C-12 (δ 177.3) there are coherent signal,1H-1H-11 (δ 4.49) and H-10 (δ in H COSY spectrum
3.22) related, determine that the group is the indole-3-lactyl group (IndLac) that C-11 hydroxyls replace.H-11 (4.49,
1H, t, J=5.3 Hz) coupling constant and compound MG30 (Nahoko Yamaji, Manabu Horikawa, Gerardo
Corzo, et al.Structure and enantioselective synthesis of polyamine toxin MG30
From the venom of the spider Macrothele gigas [J] .Tetrahedron Letters, 2004,45:
The coupling constant of corresponding H (4.53, t, J=5.5 Hz) 5371-5373.) is consistent, therefore determines that H-11 is beta comfiguration.
H-17 (δ 1.11) and C-16 (δ 67.9) in HMBC spectrum, there are coherent signal, H-14 (δ by C-14 (δ 60.1)
4.09) with C-16 (δ 67.9), C-15 (δ 173.7), C-17 (δ 20.4) there are coherent signal,1H-1H-17 (δ in H COSY spectrum
1.11) related to H-16 (δ 4.19), show that there are a Thr groups；H-35 (δ 3.89) and C-34 (δ 170.5), C-36 (δ
29.7), C-37 (δ 25.5) is there are coherent signal, H-38 (δ 3.23) and C-36 (δ 29.7), C-37 (δ 25.5), C-40 (δ
158.7) there are coherent signal, show that there are an Arg groups；The H-24 (δ 2.78) and H-25 (δ 2.78) and C- in HMBC spectrum
22 (δ 56.5), C-26 (δ 54.6) show to be connected with 2 methyl and 2 methylene on a quaternary ammonium N there are coherent signal.
There are H-14 (δ 4.09) and C-12 (δ 177.3) in HMBC spectrum, H-32 (δ 3.40,3.22) and C-34 (δ 170.5)
Correlation determines the connection type of IndLac, Thr and Arg group.
H-19 (δ 3.07) and C-21 (δ 22.2) in HMBC spectrum, H-20 (δ 1.74) and C-21 (δ 22.2), H-22 (δ
3.05) there are coherent signals with C-21 (δ 22.2), determine the carbochain of C19-C22, i.e. pass through 4 CH between N18 and N232Phase
Even；H-28 (δ 3.23) and C-27 (δ 25.5), that there are HMBC is related by H-27 (δ 1.72) and C-28 (δ 41.7) and C-26 (δ 54.6)
Signal determines the carbochain of C26-C28, i.e. passes through 3 CH between N23 and N292It is connected, H-32 (δ 3.40,3.22) and C-30 (δ
55.1), C-31 (δ 25.5), C-34 (δ 170.5) determine the carbochain of C30-C32 there are HMBC coherent signal, i.e. N29 and N33 it
Between pass through 3 CH2It is connected, and compares and determine to the related spectral data of compound Argtx-623 (compound 1 before i.e.)
Connection between N15 and N33.The parsing of comprehensive 1DNMR and 2DNMR determines the structure of the compound.
Identified, AVTX-757 is to be found to have for the first time containing an IndLac (indolelactic acid), Thr (threonine) and
The quaternary ammonium compounds of Arg (arginine), the molecular formula of the compound are C36H64O5N13, structural formula such as Figure 12.
3) functional analysis of AVTX-757
1. anesthesia and lethal effect of the AVTX-757 to insect
Through patch clamp analysis, toxin AVTX-757 can block the sodium-ion channel of blattaria when concentration is 10 μm of ol/L completely
(Figure 13) has obtained AVTX-757 pairs of toxin by the AVTX-757 of various concentration to the function analysis of blattaria sodium-ion channel
The medium effective concentration of insect DUM cell sodium channel.Wherein medium effective concentration is 0.77 ± 0.05 μm of ol/L.Toxin AVTX-
757 do not show rat sodium-ion channel in 100 μm of ol/L of concentration significantly to influence (Figure 14).Result of study shows
AVTX-757 can block completely the sodium-ion channel of insect under 10 μm of ol/L concentration, and right under up to 100 μm of ol/L concentration
Vertebrate sodium-ion channel does not have obvious effect.AVTX-757 in the research and development of neurobiological study tool reagent and drug and
The possible application of the exploitation of insecticide etc.；It is but dynamic to mammality in the sodium-ion channel of insect as a kind of selectively acting
The sodium-ion channel of object shows a possibility that AVTX-757 researches and develops guide's molecule as a kind of environment friendly agricultural without obvious effect.
Small molecule toxins AVTX-757 of the present invention has stronger insect selective toxicity, logical to insect sodium ion
The medium effective concentration in road is lower than 1 μm of ol/L.In structure be quaternary amines molecule, influenced by pH it is smaller, act on it is stronger, it is more stable.
Separating and purifying technology of the present invention has been subjected to many experiments use, it was demonstrated that feasible.Can effectively it divide from Araneus ventricosus venom
From being purified into the AVTX-757 of biological activity and other non-protein small molecule toxins.The AVTX-757's being purified into
Structure and properties analysis is repeated with the technologies such as modern biochemistry and electrophysiology, as a result reliably.Result of study shows
The present invention relates to small molecule toxins AVTX-757 be a kind of quaternary amines molecule, in previous discovery much amine toxin structure
There is notable difference, stronger to the blocking activity of insect sodium-ion channel, medium effective concentration is lower than 1 μm of ol/L.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to
So be possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features into
Row equivalent replacement；And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (7)
1. a kind of small molecule toxins isolated and purified from the thick poison of Araneus ventricosus, it is characterised in that: described slightly malicious from Araneus ventricosus
In the small molecule toxins that isolate and purify be quaternary amines small molecule toxins.
2. the small molecule toxins according to claim 1 isolated and purified from the thick poison of Araneus ventricosus, it is characterised in that: described
The relative molecular weight of the small molecule toxins isolated and purified from the thick poison of Araneus ventricosus is 757.5112, NMR structure parsing from
The molecular formula of the small molecule toxins isolated and purified in the thick poison of Araneus ventricosus is C36H64O5N13。
3. the small molecule toxins according to claim 2 isolated and purified from the thick poison of Araneus ventricosus, it is characterised in that: described
The structural formula of the small molecule toxins isolated and purified from the thick poison of Araneus ventricosus are as follows:
4. the small molecule toxins isolated and purified in the thick poison of slave Araneus ventricosus as described in claims 1 or 2 or 3 insecticide or
Application in Neurobiology reagent and/or drug.
5. the small molecule toxins isolated and purified from the thick poison of Araneus ventricosus as claimed in claim 4 are to block or block elder brother completely
The application when mode of worm sodium-ion channel is as insecticide.
6. application according to claim 5, it is characterised in that: the small molecule isolated and purified from the thick poison of Araneus ventricosus
When toxin blocks insect sodium-ion channel completely, the small molecule toxins isolated and purified from the thick poison of Araneus ventricosus using dense
Degree is not more than 10 μm of ol/L；The small molecule toxins isolated and purified from the thick poison of Araneus ventricosus are to the half of insect sodium-ion channel
Number effective concentration is not more than 1 μm of ol/L.
7. application according to claim 6, it is characterised in that: the small molecule isolated and purified from the thick poison of Araneus ventricosus
The medium effective concentration of toxin on insects sodium-ion channel is 0.77 ± 0.05 μm of ol/L.
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| CN113880930B (en) * | 2021-10-15 | 2023-06-16 | 湖南师范大学 | Polypeptide toxin THTX-Cl19 and application thereof |
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