CN104356218B - The preparation of Scolopendra subspinipes analgesia peptide precursor protein Ssm A and its product Ssm A1 and Ssm A2 and application - Google Patents
The preparation of Scolopendra subspinipes analgesia peptide precursor protein Ssm A and its product Ssm A1 and Ssm A2 and application Download PDFInfo
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Abstract
The present invention relates to the preparation of Scolopendra subspinipes analgesia peptide precursor protein Ssm A and its product Ssm A1 and Ssm A2.Scolopendra subspinipes analgesia peptide Ssm A1 and Ssm A2 has the beneficial features that structure is simple, activity is special.This Scolopendra subspinipes analgesia peptide Ssm A1 and Ssm A2 preparation method can carry out isolating and purifying obtaining from Scolopendra subspinipes venom.The present invention also provides the application of Scolopendra subspinipes analgesia peptide Ssm A1 and Ssm A2, and the two is respectively provided with the analgesic activity that many factors are led to pain, can be applicable to the preparation of pain therapy medicine.
Description
Technical field：
The present invention relates to the preparation of Scolopendra subspinipes analgesia peptide precursor protein Ssm-A and its product Ssm-A1 and Ssm-A2 and should
With belonging to biomedical sector.
Background technology
Scolopendra is important animal drug traditional simply, its Chinese medicine history of medicinal existing more than 2,000 year.Scolopendra is warm in nature, has
Poison, enters Liver Channel.Pungent-warm is dry strong, and it is violent to walk altering property, in row expression, penetrates everywhere, can search wind and removing obstruction in channels arresting convulsion, opens that expectorant row is stagnant, and the solution stasis of blood is fixed
Frightened；Also can relieve dizziness, high fever, infantile convulsions, epilepsy, etc. analgesic therapy.Detoxicating and resolving stagnation of pathogens, activating blood circulation to dissipate blood stasis and dredge the collateral, qi-restoratives Xing Yangqi flaccidity, damp eliminating dissipates evil removing toxic substances, is alone or compound recipe
Middle key medicine (Yang Meiyue etc., the status and prospects of 2012 Scolopendra externals, Chinese patent medicine, volume 34, the 7th phase, 1343-1346.).China
The function of Scolopendra subspinipes (Scolopendra subspinipes multilans) described in pharmacopeia with cure mainly for：Endogenous wind stopping town
Convulsion, removing obstruction in the collateral to relieve pain, dispersing pathogen accumulation.For liver-wind stirring up internally, spasm is twitched, infantile convulsion, middle air port fish sticking its mouth out of the water, hemiplegia, tetanus,
Rheumatoid arthritis stubborn, migraine and general headache, skin infection, scrofula, snake bite and insect sting (Chinese Pharmacopoeia Commission, 2010 Chinese Pharmacopoeias (), Beijing:
China Medical Science Press, 335-336 page).
Scolopendra subspinipes slightly poison in have phosphatase A, proteolytic enzyme, acetylcholinesterase, arginine esterase, batroxobin,
10 kinds of enzymes such as cellulase, α-amylase, hyaluronidase, alkali phosphatase and acid phosphatase, also hydroxyl peptidase, ATP enzyme,
(Tao Yong, the progress of 2000 scorpion venoms, the Chinese Biochemical Drugs such as nuotide pyrophosphatase, aminoacid naphthylamines enzyme, arginine esterase
Thing magazine, volume 21, the 2nd phase, 94-95 page).With biological to pain correlation molecule increasingly deep, disclose ion and lead to
Road plays an important role in the occurrence and development of pain.In recent years, act on Na in Scolopendra subspinipes+, K+, Ca2+Plasma leads to
The composition Study in road has considerable progress, illustrates Scolopendra subspinipes analgesic molecular basises (Yang et to a certain extent
al,2012Chemical punch packed in venoms makes centipedes excellent predators,
Mol Cell Proteomics,11:640-650；Chen et al,2014Isolation and characterization
of SsmTx-I,a Specific Kv2.1blocker from the venom of the centipede
Scolopendra Subspinipes Mutilans L.Koch,J Pept Sci.20:159-164).But in Scolopendra subspinipes with
The related material base research of its clinical removing obstruction in the collateral to relieve pain effect still is apparent not enough.
Content of the invention
It is an object of the present invention to provide Scolopendra subspinipes analgesia peptide precursor protein Ssm-A and its product Ssm-A1 and Ssm-
The preparation method of A2.Due to the difference to precursor protein Ssm-A post translational processing for the Scolopendra subspinipes poison gland, create Ssm-A1 and
The natural analgesia peptide of Ssm-A2.The difference of Ssm-A1 and Ssm-A2 is that Ssm-A1 has more at the N- end of small peptide than Ssm-A2
Asn 4 amino acid residues of Ser Lys Tyr.Ssm-A1 and Ssm-A2 have structure simple, can be by Scolopendra subspinipes slightly poison point
The beneficial features obtaining from purification.It is a further object to provide Scolopendra subspinipes analgesia peptide Ssm-A1's and Ssm-A2 should
With Ssm-A1 and Ssm-A2 is respectively provided with the strong beneficial features of analgesic activities, can be applicable to the preparation of pain therapy medicine.
Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 according to the present invention, is to separate from domestic Scolopendra subspinipes venom
Arrive, following (the SEQ ID NO of aminoacid sequence of Scolopendra subspinipes analgesia peptide Ssm-A1:2)：
Following (the SEQ ID NO of the aminoacid sequence of Scolopendra subspinipes analgesia peptide Ssm-A2:3)：
Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 that the present invention provides, its preparation method can pass through bioid credit
From purification process, obtained by Scolopendra subspinipes slightly poison.Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 of said method preparation can
Identified by mass spectrum and analgesic activities.
The preparation of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 also can be closed using chemistry by the conventional method in this area
Become or the mode of gene expression obtains, their aminoacid sequence and SEQ ID NO of the present invention:2 and SEQ ID NO:3 is identical.
The application of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 described above, described analgesia peptide Ssm-A1 and Ssm-A2 exists
Application on clinical treatment.
With prepare, there is SEQ ID NO below:1 and SEQ ID NO:The Scolopendra subspinipes analgesia of aminoacid sequence shown in 2
To illustrate as a example peptide Ssm-A1 and Ssm-A2：
Ssm-A1(SEQ ID NO:2)：
Ssm-A2(SEQ ID NO:3)：
Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 is in the experiment of mice acetic acid twisting, rat-tail illumination experiment, formaldehyde pain
Model first is mutually licked the sufficient time and is mutually licked with second and all show stronger analgesic activity in sufficient time animal model, discloses the present invention
The pain that Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 causes to many factors all has preferable analgesic effect, has and preferably faces
Bed application prospect.
The beneficial effects of the present invention is：
Therefrom obtain in domestic Scolopendra subspinipes poison gland encoding the precursor egg of 2 novel analgesia peptide Ssm-A1 and Ssm-A2
White Ssm-A, and isolate and purify Ssm-A1 the and Ssm-A2 town with good analgesic activities identifying from precursor protein Ssm-A
Pain peptide.By the Scolopendra subspinipes analgesia peptide precursor protein Ssm-A of the present invention, the aminoacid sequence of ripe analgesia peptide Ssm-A1 and Ssm-A2
Row enter line search through Protein Data Bank and compare, and find no any same protein and polypeptide.
Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 has the beneficial features that structure is simple, analgesic activity is various.
Brief description：
Fig. 1 is the G-50 sieve chromatography figure of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 of the present invention.
Fig. 2 is the ion-exchange chromatography figure of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 of the present invention.
Fig. 3 is the anti-phase C of HPLC of Scolopendra subspinipes analgesia peptide Ssm-A1 of the present invention18Column chromatography figure.
Fig. 4 is the anti-phase C of HPLC of Scolopendra subspinipes analgesia peptide Ssm-A2 of the present invention18Column chromatography figure.
Fig. 5 isolates and purifies the mass spectrum of natural Scolopendra subspinipes analgesia peptide Ssm-A1 for the present invention.
Fig. 6 isolates and purifies the mass spectrum of natural Scolopendra subspinipes analgesia peptide Ssm-A2 for the present invention.
Fig. 7 is the acetic acid twisting experimental result of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 of the present invention.
Fig. 8 is the rat-tail illumination experiment result of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 of the present invention.
Fig. 9 is that the formaldehyde-caused animal of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 of the present invention licks foot reaction the first phase
Lick sufficient time experimental result.
Figure 10 is that the formaldehyde-caused animal of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 of the present invention licks foot reaction second
Mutually lick sufficient time experimental result.
Specific embodiment
Embodiment 1：The primary structure of Scolopendra subspinipes analgesia peptide precursor protein Ssm-A measures
1.1st, Scolopendra subspinipes poison gland transcript profile measures
Scolopendra subspinipes live body picks up from Suizhou, hubei, 4 individualities of random choose, and under stereomicroscope, 4 degree separate Scolopendra subspinipes
Poison gland, is immediately placed in liquid nitrogen flash freezer.Then transported with dry ice and carry out Scolopendra subspinipes poison gland transcription to BGI-Shenzhen
Group sequencing.The major experimental step that commercialization Scolopendra subspinipes transcript profile measures is as follows：Extract Scolopendra subspinipes poison gland sample total serum IgE simultaneously
After DNaseI digestion DNA, with the enrichment with magnetic bead eukaryote mRNA with Oligo (dT)；Addition interrupts reagent and exists
In Thermomixer, mRNA is broken into short-movie section by thermophilic, and the mRNA after to interrupt is templated synthesis one chain cDNA, then prepares
Two chain synthesis reaction systems synthesize two chain cDNA, and are added using the 3' end of kits recovery, sticky end reparation, cDNA
Upper base " A " jointing, then carry out Piece Selection, finally enter performing PCR amplification；The library Agilent building
After 2100Bioanalyzer and ABI StepOnePlus Real-Time PCR System quality inspection is qualified, using Illumina
HiSeqTM 2000 is sequenced.
1.2nd, Scolopendra subspinipes analgesia peptide precursor protein Ssm-A primary structure
The transcription notebook data that above-mentioned steps 1 obtain, after gene order assembling and gene expression analysis, has obtained few spine Wu
Overall amino acid sequence ((the SEQ ID NO of centipede analgesia peptide precursor protein Ssm-A:1)：
The Scolopendra subspinipes analgesia peptide precursor protein Ssm-A complete sequence of the present invention enters line search through Protein Data Bank and compares,
Find no any same protein molecule.
Embodiment 2：Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 isolating and purifying and identifying
2.1st, isolate and purify
Scolopendra subspinipes live body picks up from Suizhou, hubei, takes its venom (being dissolved in normal saline), vacuum freezing with electrostimulation
It is dried, -80 ° save backup.
The first step：Sephadex G-50 molecular sieve：Obtain venom lyophilized powder according to the method described above, be dissolved in deionized water
In, take and use 20mM Tris-HCl buffer (pH=7.8, NaCl containing 0.1M) to balance in advance on 1ml (protein content is 100mg)
Sephadex G-50 (GE Healthcare, the ultra-fine) pillar (length 122cm, internal diameter width 1.4cm) of 24 hours, with same
Buffer carry out eluting, flow velocity is 1.5ml/10min, and every 10min collects once, measures its absorbance under 280nm, institute
Obtain isolates and purifies collection of illustrative plates as shown in figure 1, wherein Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 is present in the 4th peak, sees Fig. 1 arrow
Peak shown in head.
Second step：Resource S cation-exchange chromatography：Sample acquired in the first step is through HPLC C8Post desalination,
Vacuum lyophilization obtains lyophilized powder, then uses A liquid (20mM HAc-NaAc, pH=4.0) to dissolve, passes throughExplore
The system of isolating and purifying is isolated and purified.Sample is splined on the Resource S cation exchange column (GE being balanced in advance with A liquid
Healthcare product, 1ml) under conditions of flow velocity is for 1ml/min, with B liquid (20mM HAc-NaAc, pH=4.0,1M
NaCl under linear gradient (0-100%in 100min)) carry out eluting, monitoring wavelength is 215nm.Gained isolate and purify figure
As shown in Fig. 2 Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 is located at the 7th peak and the 5th peak in Fig. 2 respectively, see Fig. 2 arrow institute
Show.
3rd step：High performance liquid chromatography reversed phase chromatography：
The purification of Scolopendra subspinipes analgesia peptide Ssm-A1：It is dissolved in deionized water after second step the 7th peak sample vacuum lyophilization
It is splined on Hypersil ODS25mm pillar (the Erie's special product having been balanced with ultra-pure water (trifluoracetic acid containing 0.1%) in advance afterwards
Product, a size of 4.6mm × 300mm), experimental apparatus are Waters 1525 high-pressure liquid phase system, in the bar for 1ml/min for the flow velocity
Under part, carry out eluting with acetonitrile (trifluoracetic acid containing 0.1%) under the conditions of linear gradient (0-100%in 100min), monitoring
Wavelength is 215nm, gained isolate and purify collection of illustrative plates as shown in figure 3, in figure arrow show the natural Scolopendra subspinipes analgesia of purification
Peptide Ssm-A1.
The purification of Scolopendra subspinipes analgesia peptide Ssm-A2：It is dissolved in deionized water after second step the 5th peak sample vacuum lyophilization
It is splined on Hypersil ODS25 m pillar (the Erie's special product having been balanced with ultra-pure water (trifluoracetic acid containing 0.1%) in advance afterwards
Product, a size of 4.6mm × 300mm), experimental apparatus are Waters 1525 high-pressure liquid phase system, in the bar for 1ml/min for the flow velocity
Under part, carry out eluting with acetonitrile (trifluoracetic acid containing 0.1%) under the conditions of linear gradient (0-100%in 100min), monitoring
Wavelength is 215nm, gained isolate and purify collection of illustrative plates as shown in figure 4, in figure arrow show the natural Scolopendra subspinipes analgesia of purification
Peptide Ssm-A2.
2.2nd, Molecular Identification
The mensure of aminoacid sequence：
Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 that purification obtains is in full-automatic protein sequencing instrument (Shimadzu
PPSQ-31A through Edman edman degradation Edman on), determine the aminoacid total order of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 respectively
Row, result shows that Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 is respectively provided with SEQ ID NO of the present invention:2 and SEQ ID NO:3
Shown structure.
Mass spectroscopy molecular measures fixed：
Substance assistant laser desorpted flight time mass spectrum (MALDI-TOF-MS) have detected the Scolopendra subspinipes town that purification obtains
The accurate molecular weight of pain peptide Ssm-A1 and Ssm-A2, instrument is Bruker company Autoflex III TOF/TOF mass spectrum
Instrument.The molecular weight of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 mass spectroscopy is respectively 3460.4 dalton and 3130.4 dongle
, as shown in Fig. 5 and Fig. 6.Mass spectral results disclose 4 cysteine in Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 molecule
Residue has been respectively formed intramolecular disulfide bond, and Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 no free cysteine exists.
Embodiment 3：The analgesic activities of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 measure
For understanding the analgesic activities of Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 in depth, the present invention utilizes different pain
Animal model is studied, and result shows Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 in different animal pain models
All show stronger analgesic activities, be described below：
3.1st, the analgesic activity to mice acetic acid twisting pain model for Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2：
Laboratory animal adopts SPF level Male Kunming strain mice (body weight 18-22g).Purification Scolopendra subspinipes analgesia peptide Ssm-A1
It is dissolved separately in physiological saline solution with Ssm-A2, lumbar injection (100 μ l) variable concentrations Scolopendra subspinipes town on the left of laboratory animal
After pain peptide Ssm-A1 or Ssm-A230 minute, the acetic acid of right side lumbar injection 100 μ l 0.6%, count 30 after injected in mice acetic acid
The writhing number of times of minute.Using normal saline as negative control, morphine, as positive control, with 6 mices is every time for this experiment
Experimental subject, is repeated 3 times.The analgesic activity to mice acetic acid twisting pain model for Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2
As shown in Figure 7.
Test result indicate that：Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 all can reduce the torsion of mice acetic acid in dose-dependant ground
Body number of times, has manifested the analgesic effect that Dichlorodiphenyl Acetate causes ANIMAL PAIN.
3.2nd, the analgesic activity to Mouse Light pain model for Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2
The SPF level Kun Ming mice selecting body weight 18-22g carries out primary dcreening operation, and the qualified mice of primary dcreening operation is used for subsequent experimental.To close
Lattice mice loads in fixed cylinder, and adjusting its position makes rat-tail point in tail point position line, and rat-tail is placed in photo-electric control probe
Between, rat-tail dolorimeter (model：YLS-12A, Huaibei Zhenghua Biological Instrument Co., Ltd.) infrared beam impinge upon apart from little
At the 1/3 of Mus tail base.Start to measure, illumination power is 35W, accepts infrared beam from mice and is irradiated to after mice peace and quiet
There is the time interval between whipping action as the threshold of pain in mice.Mice between 3～7s for the selection threshold of pain, random packet, often
Group 6.Abdominal cavity injects 100 μ l variable concentrations Scolopendra subspinipes analgesia peptide Ssm-A1 or Ssm-A2 sample, injected sample 30min respectively
Measure the pain threshold of mice afterwards.Using normal saline as negative control, morphine as positive control, every time with 6 mices as reality
Test object, be repeated 3 times.Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 analgesic activity such as Fig. 8 to Mouse Light pain model
Shown.
Test result indicate that：Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 all energy dose-dependant ground deferred lightings cause
Mice whipping number of times, has manifested the analgesic effect that illumination is caused with ANIMAL PAIN.
3.3rd, analgesic activity in formaldehyde in mice pain model for Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2
Test adopts male mouse of kunming (18-22g), and sample lyophilized powder is dissolved in physiological saline solution, using abdominal cavity
Injection system is administered, and matched group gives the physiological saline solution of same volume.Half an hour after administration, behind the mice right side, vola is adopted
Use hypodermic mode, the formaldehyde of every injected in mice 20 μ l 2.5%, count 0-5 minute after injected in mice formaldehyde respectively
(the second phase, because local chronic is scorching for (the first phase is directly to stimulate acute pain caused by teleneuron by formaldehyde) and 20-30min
The nociceptive information that disease leads to is constantly incoming the inflammatory pain causing) lick the sufficient time.This experiment is right as feminine gender using normal saline
According to morphine, as positive control, every time with 6 mices as experimental subject, is repeated 3 times.Scolopendra subspinipes analgesic polypeptide Ssm-A1 and
The analgesic activity of Ssm-A2 is as shown in Figure 9 and Figure 10.
Experimental result explanation：It is acute that Scolopendra subspinipes analgesia peptide Ssm-A1 and Ssm-A2 causes to formaldehyde in mice pain model
(the first phase) and inflammatory pain (the second phase) all have preferable analgesic activities bitterly.
<110>Kunming Institute of Zoology, Chinese Academy of Sciences
<120>The preparation of Scolopendra subspinipes analgesia peptide precursor protein Ssm-A and its product (Ssm-A1, Ssm-A2) and application
<160> 3
<210> 1
<211> 69
<212> PRT
<213>Scolopendra subspinipes（Scolopendra subspinipes mutilans）
<400> 1
Met Met Leu Lys Ser Phe Cys Ile Leu Ser
1 5 10
Val Phe Met Val Leu Phe Leu Ala Lys Phe
15 20
Pro Asp Leu Cys Ser Gly Glu Glu Ile Ser
25 30
Pro Leu Lys Ile Val Val Arg Asn Ser Lys
35 40
Tyr Leu Asn Asn Pro Cys Asn Gly Val Thr
45 50
Cys Pro Ser Gly Tyr Arg Cys Ser Ile Val
55 60
Asp Lys Gln Cys Ile Lys Lys Glu Lys
65
<210> 2
<211> 31
<212> PRT
<213>Scolopendra subspinipes（Scolopendra subspinipes mutilans）
<400> 2
Asn Ser Lys Tyr Leu Asn Asn Pro Cys Asn
1 5 10
Gly Val Thr Cys Pro Ser Gly Tyr Arg Cys
15 20
Ser Ile Val Asp Lys Gln Cys Ile Lys Lys
25 30
Glu
31
<210> 3
<211> 27
<212> PRT
<213>Scolopendra subspinipes（Scolopendra subspinipes mutilans）
<400> 3
Leu Asn Asn Pro Cys Asn Gly Val Thr Cys
1 5 10
Pro Ser Gly Tyr Arg Cys Ser Ile Val Asp
15 20
Lys Gln Cys Ile Lys Lys Glu
25
Claims (7)
1. Scolopendra subspinipes analgesia peptide precursor protein Ssm-A it is characterised in that：Described analgesia peptide precursor protein Ssm-A is by following sequences
Aminoacid sequence SEQ ID NO in list:Shown in 1：
Met Met Leu Lys Ser Phe Cys Ile Leu Ser 10
Val Phe Met Val Leu Phe Leu Ala Lys Phe 20
Pro Asp Leu Cys Ser Gly Glu Glu Ile Ser 30
Pro Leu Lys Ile Val Val Arg Asn Ser Lys 40
Tyr Leu Asn Asn Pro Cys Asn Gly Val Thr 50
Cys Pro Ser Gly Tyr Arg Cys Ser Ile Val 60
Asp Lys Gln Cys Ile Lys Lys Glu Lys 69.
2. Scolopendra subspinipes analgesia peptide precursor protein Ssm-A bioactive natural product Ssm-A1 it is characterised in that：Described analgesia peptide by
Aminoacid sequence SEQ ID NO in following sequence tables:Shown in 2：
Asn Ser Lys Tyr Leu Asn Asn Pro Cys Asn 10
Gly Val Thr Cys Pro Ser Gly Tyr Arg Cys 20
Ser Ile Val Asp Lys Gln Cys Ile Lys Lys 30
Glu 31.
3. Scolopendra subspinipes analgesia peptide precursor protein Ssm-A bioactive natural product Ssm-A2 it is characterised in that：Described analgesia peptide by
Aminoacid sequence SEQ ID NO in following sequence tables:Shown in 3：
Leu Asn Asn Pro Cys Asn Gly Val Thr Cys 10
Pro Ser Gly Tyr Arg Cys Ser Ile Val Asp 20
Lys Gln Cys Ile Lys Lys Glu 27.
4. Scolopendra subspinipes analgesia peptide Ssm-A1 or Ssm-A2 described in Claims 2 or 3 preparation method it is characterised in that：Can be from
Separate in Scolopendra subspinipes venom and obtain, separated Ssm-A1 and Ssm-A2 analgesia peptide is respectively provided with by SEQ ID NO:2 and SEQ
ID NO:Aminoacid sequence shown in 3.
5. Scolopendra subspinipes analgesia peptide Ssm-A1 described in claim 2 application it is characterised in that：Described Scolopendra subspinipes analgesia peptide
Application in preparing pain therapy medicine for the Ssm-A1.
6. Scolopendra subspinipes analgesia peptide Ssm-A2 described in claim 3 application it is characterised in that：Described Scolopendra subspinipes analgesia Ssm-
Application in preparing pain therapy medicine for the A2.
7. Scolopendra subspinipes analgesia peptide Ssm-A1 or Ssm-A2 described in claim 4 application it is characterised in that：Described Scolopendra subspinipes
Application in preparing pain therapy medicine for analgesia peptide Ssm-A1 or Ssm-A2.
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| CN105085646A (en) * | 2015-07-14 | 2015-11-25 | 中国科学院昆明动物研究所 | Centipede analgesic peptide SLP_RhTx and gene and application thereof |
| CN108840927B (en) * | 2018-06-06 | 2022-07-29 | 湖南生达生物科技有限公司 | Elastase inhibitor LNSP-I and application thereof |
| CN112521457B (en) * | 2020-12-29 | 2022-03-01 | 潍坊医学院 | Analgesic peptide CI118 separated from cinobufotalin injection and application thereof |
| CN118005744A (en) * | 2022-11-09 | 2024-05-10 | 浙江大学 | Polypeptide with analgesic effect and application thereof |
| CN116769007B (en) * | 2023-07-24 | 2024-02-20 | 东北林业大学 | Centipede analgesic polypeptide PvTx and encoding gene and application thereof |
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| KR101444257B1 (en) * | 2013-04-11 | 2014-09-26 | 대한민국 | A new scolopendrasin ii peptide isolated from the scolopendra subsinipes and its synthetic composition |
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