CN101824074A - Micro-assisted solid-phase synthesis of analogue of MC-JJ0107 polypeptide isolated from Momordica charantia and application of the analogue - Google Patents
Micro-assisted solid-phase synthesis of analogue of MC-JJ0107 polypeptide isolated from Momordica charantia and application of the analogue Download PDFInfo
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- CN101824074A CN101824074A CN201010177944A CN201010177944A CN101824074A CN 101824074 A CN101824074 A CN 101824074A CN 201010177944 A CN201010177944 A CN 201010177944A CN 201010177944 A CN201010177944 A CN 201010177944A CN 101824074 A CN101824074 A CN 101824074A
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- 235000013311 vegetables Nutrition 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to a novel, high-efficiency and blood sugar-lowering analogue of MC-JJ0107 polypeptide isolated from Momordica charantia and a micro-assisted solid-phase synthesis method thereof. The analogue of the MC-JJ0107 polypeptide with longer pharmacologic action time is obtained by modifying positions 1, 3, 4, 7 or 8 of a polypeptide of natural Momordica charantia; the chemical synthesis of the analogue can be efficiently and quickly realized by the micro-assisted solid-phase synthesis method, wherein the analogue of the MC-JJ0107 polypeptide is obtained by purifying a crude product with a preparative high-efficiency liquid phase and freeze-drying the purified product.
Description
Technical field
The present invention relates to MC-JJ0107 polypeptide analog and microwave thereof and promote solid phase synthesis process.
Background technology
Diabetes are important diseases of current harm humans health, and the whole world has the people of 5%-7% to be subjected to diabetes mellitus approximately at present, is considered to after cardiovascular and cerebrovascular diseases, malignant tumour, cause human wounded or disabled, dead the third-largest killer.
Diabetes are divided into I type and II type, and type i diabetes is a kind of autoimmune disease, and patient's survival needs insulin injection.Type ii diabetes accounts for about 95% of numerous diabetic subject's sums.The reason of type ii diabetes is an islet cells metabolism generation obstacle, hypoinsulinism, perhaps producing insulin resistant, is to be main companion's insulin secretion relative deficiency with the insulin resistant, serves as the metabolic disease that main companion's insulin resistant causes with the insulin secretion relative deficiency perhaps.Hypoinsulinism perhaps produces insulin resistant and all can cause in the blood glucose excessive, and when blood-sugar content surpasses the kidney presentation time, glucose is just transferred in the urine and discharged, thereby produces dextrosuria.
Balsam pear (Momordica charantia) is that a kind of mankind have the edible historical vegetables of long-term safety.Recent two decades comes, people have found many compositions with hypoglycemic activity in the fruit of balsam pear, polypeptide composition wherein obtains people's understanding gradually and obtains some utilizations, but because the extraction separation of bitter gourd polypeptide is too complicated, cost is higher to be difficult to obtain pure polypeptide again, and we use modern peptide synthesis technology to address this problem now.
Polypeptide can obtain by the method for engineered method or chemosynthesis.Engineered method has superiority than chemical process obtaining on long peptide (amino-acid residue length is greater than 50) or the protein, but the chemical synthesis process of polypeptide is especially after the solid phase synthesis strategy occurs, handiness, diversity and the high efficiency etc. that have gene engineering method to hardly match on less than 40 polypeptide or little peptide in preparation amino-acid residue length.Merrifield in 1963 found and have developed the method for solid-phase synthetic peptide.Solid-phase polypeptide is synthetic generally two kinds of strategies: i.e. Boc/Bzl orthogonally protect solid phase synthesis strategy and Fmoc/tBu orthogonally protect solid phase synthesis strategy, the solid-phase synthesis that Merrifield foundes is Boc/Bzl orthogonally protect solid phase synthesis strategy.But, have some shortcomings in the Boc/Bzl orthogonally protect solid phase synthesis strategy, many as side reaction, condition is harsh and in the process of prolongation peptide chain polypeptide chain can lose from solid phase etc.The Fmoc/tBu orthogonally protect solid phase synthesis strategy of Chu Xianing reaction conditions gentleness many then subsequently.After microwave technology applies in the solid phase synthesis of polypeptide in recent years, make the synthetic technology of polypeptide produce a leap.Microwave promotes chemical reaction to be because it makes polar molecule fast rotational in microwave field, makes fast 10 to 1000 times of the more conventional heating means of some speed of reaction, and productive rate improves greatly.People's reported first such as Gedye in 1986 with microwave application in organic synthesis, microwave can promote many chemical reactions, as the Diels-Alder reaction, saponification reaction etc. can be accelerated speed of reaction significantly and improve yield.In 1992, Hui-ming Yu etc. reported at first with microwave application that in polypeptide solid phase synthesis field they have finished the synthetic of acyl carrier protein segment decapeptide (acyl carrier protein, ACP 65～74).
How synthetic efficiently long peptide (greater than 20 peptides) remain a challenge in the world, because polypeptide is along with the increase of peptide chain, its synthetic difficulty is multiplied.With the synthetic long peptide of traditional solid phase method, the more purification difficult of the often very low impurity of its yield, thereby say from practical angle and to have lost the synthetic meaning.Secondly synthesis cycle is long, and 30 peptides nearly time in a week of general needs just can not finished synthesis cycle under the centre does not encounter difficulties the situation of peptide preface, if difficult peptide preface, often just can't synthesize and obtains target polypeptides.And use microwave to promote solid-phase synthetic peptide, can overcome difficulties the peptide preface, the polypeptide that synthetic traditional solid phase method can't obtain, and generated time shortens greatly, and significantly improve polypeptide crude product purity and yield, make that the purifying of product is convenient greatly, as long as just can obtain the purity high product through a preparation HPLC; Can carry out pointed decoration with D type amino acid and alpha-non-natural amino acid etc. to polypeptide very easily in addition, remove to seek active higher, polypeptide that biological half-life is longer, this especially genetic engineering technique can't accomplish.Therefore, our employing this kind method synthetic MC-JJ0107 serial analogs that obtains rapidly and efficiently in balsam pear hypoglycemic (MC-JJ0107) polypeptide analog synthetic.
Polypeptide can obtain by the method for engineered method or chemosynthesis.Engineered method has superiority than chemical process obtaining on long peptide (amino-acid residue length is greater than 50) or the protein, but the chemical synthesis process of polypeptide is especially after the solid phase synthesis strategy occurs, handiness, diversity and the high efficiency etc. that have gene engineering method to hardly match on less than 40 polypeptide or little peptide in preparation amino-acid residue length.Merrifield in 1963 found and have developed the method for solid-phase synthetic peptide.Solid-phase polypeptide is synthetic generally two kinds of strategies: i.e. Boc/Bzl orthogonally protect solid phase synthesis strategy and Fmoc/tBu orthogonally protect solid phase synthesis strategy, the solid-phase synthesis that Merrifield foundes is Boc/Bzl orthogonally protect solid phase synthesis strategy.But, have some shortcomings in the Boc/Bzl orthogonally protect solid phase synthesis strategy, many as side reaction, condition is harsh and in the process of prolongation peptide chain polypeptide chain can lose from solid phase etc.The Fmoc/tBu orthogonally protect solid phase synthesis strategy of Chu Xianing reaction conditions gentleness many then subsequently.After microwave technology applies in the solid phase synthesis of polypeptide in recent years, make the synthetic technology of polypeptide produce a leap.Microwave promotes chemical reaction to be because it makes polar molecule fast rotational in microwave field, makes fast 10 to 1000 times of the more conventional heating means of some speed of reaction, and productive rate improves greatly.People's reported first such as Gedye in 1986 with microwave application in organic synthesis, microwave can promote many chemical reactions, as the Diels-Alder reaction, saponification reaction etc. can be accelerated speed of reaction significantly and improve yield.In 1992, Hui-ming Yu etc. reported at first with microwave application that in polypeptide solid phase synthesis field they have finished the synthetic of acyl carrier protein segment decapeptide (acyl carrier protein, ACP 65～74).
How synthetic efficiently long peptide (greater than 30 peptides) remain a challenge in the world, because polypeptide is along with the increase of peptide chain, its synthetic difficulty is multiplied.With the synthetic long peptide of traditional solid phase method, the more purification difficult of the often very low impurity of its yield, thereby say from practical angle and to have lost the synthetic meaning.Secondly synthesis cycle is long, and 30 peptides nearly time in a week of general needs just can not finished synthesis cycle under the centre does not encounter difficulties the situation of peptide preface, if difficult peptide preface, often just can't synthesize and obtains target polypeptides.And use microwave to promote solid-phase synthetic peptide, can overcome difficulties the peptide preface, the polypeptide that synthetic traditional solid phase method can't obtain, and generated time shortens greatly, and significantly improve polypeptide crude product purity and yield, make that the purifying of product is convenient greatly, as long as just can obtain the purity high product through a preparation HPLC; Can carry out pointed decoration with D type amino acid and alpha-non-natural amino acid etc. to polypeptide very easily in addition, remove to seek active higher, polypeptide that biological half-life is longer, this especially genetic engineering technique can't accomplish.Therefore, our employing this kind method synthetic MC-JJ0107 serial analogs that obtains rapidly and efficiently in balsam pear hypoglycemic (MC-JJ0107) polypeptide analog synthetic.
Summary of the invention
The present invention has two first mothers of purpose is to obtain polypeptide to modify and obtain the higher MC-JJ0107 polypeptide analog of hypoglycemic activity from the medicinal and edible plant balsam pear of tool hypoglycemic activity.
Second purpose of the present invention provided the method for preparing solid phase of MC-JJ0107 derivative, and the present invention adopts microwave to promote Fmoc/tBu orthogonally protect solid phase synthesis strategy efficiently to synthesize apace and obtains serial MC-JJ0107 analogue.
It is characterized in that: adopt microwave to promote Fmoc/tBu orthogonally protect solid phase synthesis strategy, earlier syntheticly on solid phase carrier obtain being loaded with first Fmoc and protect amino acid whose resin, ninhydrin method detects sloughs the resin that the Fmoc protecting group obtains being loaded with first amino-acid residue after negative; Enter next coupling circulation again; repeat the step of coupling and deprotection with different protection amino acid according to corresponding peptide preface; prolong required aminoacid sequence successively, the synthetic resin that obtains being loaded with corresponding polypeptide cuts down polypeptide with cracking agent at last and obtains the polypeptide crude product from resin.Crude product is through the preparation scale high-efficient liquid phase chromatogram purification, and freeze-drying gets the pure product of polypeptide.
Be loaded with the preparation method that first Fmoc protects amino acid whose resin; it is characterized in that by obtaining with the solid phase carrier coupling again after the activated dose of activation earlier of Fmoc protection amino acid under the microwave irradiation condition; add 1-hydroxyl-benzotriazole (HOBT) or derivatives thereof in the reaction and suppress racemization, and use the acidity of organic bases neutralization reaction.Being loaded with first Fmoc, to protect the employed solid phase carrier of amino acid whose resin be Rink resin, Wang resin or 2-chlorine trityl chloride resin.Activator is dicyclohexylcarbodiimide (DCC), N, N '-DIC (DIC), N, N " carbonyl dimidazoles (CDI); 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC.HCl); 2-(7-azo benzotriazole)-N; N; N '; N '-tetramethyl-urea phosphofluoric acid ester (HATU), benzotriazole-N, N, N ', N '-tetramethyl-urea phosphofluoric acid ester (HBTU) or 1-hydroxyl-benzotriazole (HOBT) derivative that uses are N-hydroxy-succinamide (HOSU), 1-hydroxyl-7-azo benzotriazole (HOAT) or 3-hydroxyl-1,2,3-phentriazine-4 (3H)-ketone (HOOBT).Organic bases is triethylamine (TEA), N-methylmorpholine (NMM) or diisopropylethylamine (DIEA); Microwave promotion condition is: microwave frequency 2450MHz, temperature of reaction: 20～100 ℃, the reaction times is 5～15min.
Removing of Fmoc protecting group is to contain 0.1mol.L by use
-1Hexahydropyridine solution reaction under microwave promotes of 1-hydroxyl-benzotriazole (HOBT), selecting dimethyl formamide (DM F), methyl-sulphoxide (DMSO) or N-Methyl pyrrolidone (NMP) for use is reaction solvent.Microwave promotion condition is: microwave frequency 2450MHz, temperature of reaction: 20～100 ℃, the reaction times is 1～10min.
The invention has the advantages that:
1. a kind of MC-JJ0107 analogue of Ti Chuing can improve the stability of MC-JJ0107 on the basis that keeps hypoglycemic activity, prolongs action time.
2. microwave promotes solid phase synthesis MC-JJ0107 analogue to improve coupled reaction speed greatly, and amino acid of the abundant coupling of conventional solid phase synthesis process goes to resin, often needs do not wait by 20 hours in 2 hours, even longer.Microwave promotes then average to need about 10 minutes; Conventional solid phase synthesis process takes off the Fmoc protecting group, often needs do not wait by 1 hour in 30 minutes, and microwave promotes then on average only to need about 5 minutes, and this has improved polypeptide synthetic efficient greatly, has shortened synthesis cycle.
3. microwave promotes the purity of the synthetic crude product that obtains of solid phase synthesis MC-JJ0107 analogue greater than 80%, more conventional solid phase synthesis process improves greatly, this has made things convenient for follow-up purifying work, only need be through once preparing the liquid phase purifying, and freeze-drying can obtain the pure product of target.
4. microwave promotes the synthetic MC-JJ0107 analogue of solid phase method, and its cost is low because coupling efficiency is higher, required protection amino acid is average only need 2 times excessive, more conventional solid phase synthesis process needs 4 to 5 times excessively greatly to reduce.
5. microwave promotes solid phase synthesis MC-JJ0107 analogue method easily to be automated, to change on a large scale, and this makes it be more suitable for suitability for industrialized production.
Therefore promote the MC-JJ0107 analogue that solid phase synthesis technique prepares with microwave provided by the invention, the yield height, synthesis cycle is short, purifying crude is easy, and production cost is low, be easy to industrial automation production.The MC-JJ0107 analogue for preparing, more stable than natural MC-JJ0107, be suitable as the activeconstituents for the treatment of diabetes medicament.
Embodiment
Adopt following abbreviation in this specification:
Et
3N: triethylamine; The NMM:N-methylmorpholine; DIEA:N, N '-diisopropylethylamine; DMF: dimethyl formamide; DM SO: methyl-sulphoxide; DCM: methylene dichloride; The Fmoc:N-9 fluorenylmethyloxycarbonyl; DIC:N, N '-DIC; CDI:N, N '-carbonyl dimidazoles; The DMAP:4-Dimethylamino pyridine; The HOSU:N-N-Hydroxysuccinimide; EDC.HCl:1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride; HATU:2-(7-azo benzotriazole)-N, N, N ', N '-tetramethyl-urea phosphofluoric acid ester; HBTU: benzotriazole-N, N, N ', N '-tetramethyl-urea phosphofluoric acid ester; HCTU:6-chlorobenzene and triazole-1,1,3,3-tetramethyl-urea phosphofluoric acid ester; HOAT:1-hydroxyl-7-azo benzotriazole; HOBT:1-hydroxyl-benzotriazole; PyBOP: phosphofluoric acid benzotriazole-1-base-oxygen base tripyrrole alkyl phosphorus; HPLC: high performance liquid chromatography; ESI-MS: electrospray ionization mass spectrum; Gly: glycine; Ser: Serine; Ala: L-Ala; Thr: Threonine; Val: Xie Ansuan; Ile: Isoleucine; Leu: leucine; Tyr: tyrosine; Phe: phenylalanine; His: Histidine; Pro: proline(Pro); Asp: aspartic acid; Met: methionine(Met); Glu: L-glutamic acid; Trp: tryptophane; Lys: Methionin; Arg: arginine.Asn: l-asparagine; Gln: glutamine.
The present invention describes by following implementation column, but these embodiment do not do any restriction explanation of the present invention.
Embodiment 1
The microwave of Ala-Pro-Ala-Ala-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:2) promotes solid phase synthesis
(1) swelling of resin
Take by weighing Fmoc-rink amide-MBHA Resin 50mg (replacement amount 0.4mmol/g), through 7mL DCM swelling 30min, suction filtration removes DCM, uses 10mL NMP swelling 30min again, uses NMP at last respectively, DCM, and NMP 7mL rinses well.
(2) microwave promotes removing of Fmoc protecting group
The resin that swelling is good is put into reactor, adds 25% piperidines/NMP (V/V) solution that 7mL contains 0.1M HOBT, reacts 1min in microwave reactor, microwave power is 15W, temperature of reaction is controlled in 50 ℃, uses the cooling of air compressor pressurized air, and reaction finishes back elimination solution; Add 25% piperidines/NMP (V/V) solution that 7mL contains 0.1M HOBT again and react 4min again in microwave reactor, microwave power is 25W, and temperature of reaction is controlled at 50 ℃, uses the cooling of air compressor pressurized air.Reaction finishes back elimination solution, uses the NMP washes clean.Obtain sloughing the resin of the Fmoc protecting group of initial connection.
(3) microwave promotes synthesizing of Fmoc-Ser-rink amide-MBHA Resin
With Fmoc-Ser-OH (0.04mmol), HBTU (0.04mmol), HOBT (0.04mmol) and DIPEA (0.08mmol) are dissolved among the 10mL NMP, in the resin above again this solution being added, in microwave reactor, react 7min, microwave power is 25W, and temperature of reaction is controlled at 50 ℃., use the cooling of air compressor pressurized air.Reaction finishes back filtering reaction solution, uses DCM and each 7mL washing resin of NMP 3 times.
(4) detection of coupling efficiency
With the coupling efficiency of ninhydrin method or bromjophenol blue method qualitative detection resin, color reaction is negative can to enter next coupling circulation.
Ninhydrin method: the resin particle washing with alcohol takes a morsel, put into transparent bottle and add respectively 2 of 5% triketohydrindene hydrate ethanol, KCN pyridine solution (2ml 0.001MKCN is diluted in the 98ml pyridine), 80% phenol ethanolic solns, in 100 ℃ of heating 5 minutes, promptly positive if resin shows blueness.
The bromjophenol blue method: the resin particle that takes a morsel washs with two formyl ethanamides, puts into the tetrabromophenol sulfonphthalein dimethylacetamide solution that transparent bottle adds 3 1%, and jolting is 3 minutes under the normal temperature, and is promptly positive if resin shows blueness.
(5) prolongation of peptide chain
According to Ala
1-MC-JJ0107-(1～9)-NH
2Sequence, the steps in sequence that repeats above-mentioned deprotection and coupling is connected corresponding amino acid, the coupling microwave promotes reaction times 5～20min not wait.Obtain being connected with Ala
1-MC-JJ0107-(1～9)-NH
2Resin.
(6) cracking of polypeptide on the resin
With above-mentioned obtain be connected with Ala
1-MC-JJ0107-(1～9)-NH
2Resin put into reaction flask, each adds cracking agent Reagent K, and (TFA/ thioanisole/water/phenol/EDT, 82.5: 5: 5: 5: 2.5, V/V) 10mL earlier at 0 ℃ of following jolting 30min, reacted 3h more at normal temperatures.Reaction finishes the back suction filtration, adds a small amount of TFA and DCM washing three times, merging filtrate.Filtrate added in a large amount of ice ether separate out white flocks, frozen centrifugation obtains the crude product of target polypeptides.Finally obtain Ala
1-MC-JJ0107-(1～9)-NH
2Crude product 63.2mg, yield are 94.3%.
(7) Ala
1-MC-JJ0107-(1～9)-NH
2The purifying of crude product
With Ala1-MC-JJ0107-(1～the 9)-NH that obtains above
2Crude product is dissolved in a spot of water, prepares type reversed-phase HPLC purifying crude product with Tianjin, island.Adopt the anti-phase preparative column of C18 (340mm * 28mm, 5 μ m) in the purifying; Mobile phase A: 0.1%TFA/ water (V/V), Mobile phase B: 0.1%TFA/ acetonitrile (V/V); Eluent gradient: Mobile phase B 20%～65%, 40min; Flow velocity is 6mL/min; The detection wavelength is 214nm.The solution freeze-drying of collecting gets pure product, finally obtains pure product 29.7mg.Theoretical relative molecular mass 814.9ESI-MSm/z:found[M+3H]
3+272.6, [M+4H]
4+204.5, [M+5H]
5+164.1; Calu[M+3H]
3+272.6, [M+4H]
4+204.7, [M+5H]
5+164.0
According to embodiment 1 described method, according to the synthetic polypeptide that obtains embodiment 2～49 of corresponding sequence, by electrospray ionization mass spectrum (ESI-MS) conclusive evidence molecular weight separately.
Embodiment 2
Ala-Pro-Ala-Cys-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:3); Theoretical relative molecular mass 847.0
ESI-MSm/z：found[M+3H]
3+283.4，[M+4H]
4+212.6，[M+5H]
5+170.5；calu[M+3H]
3+283.3，[M+4H]
4+212.7，[M+5H]
5+170.4
Embodiment 3
Ala-Pro-Ala-Gly-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:4); Theoretical relative molecular mass 800.9
ESI-MSm/z：found[M+3H]
3+268.0，[M+4H]
4+201.2，[M+5H]
5+161.3；calu[M+3H]
3+268.0，[M+4H]
4+201.2，[M+5H]
5+161.2
Embodiment 4
Ala-Pro-Ala-His-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:5); Theoretical relative molecular mass 881.0
ESI-MSm/z：found[M+3H]
3+294.7，[M+4H]
4+221.3，[M+5H]
5+177.3；calu[M+3H]
3+294.7，[M+4H]
4+221.2，[M+5H]
5+177.2
Embodiment 5
Ala-Pro-Ala-Lys-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:6); Theoretical relative molecular mass 872.0
ESI-MSm/z：found[M+3H]
3+291.7，[M+4H]
4+219.2，[M+5H]
5+175.6；calu[M+3H]
3+291.7，[M+4H]
4+219.0，[M+5H]
5+175.4
Embodiment 6
Ala-Pro-Ala-Tyr-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:7); Theoretical relative molecular mass 907.0
ESI-MSm/z：found[M+3H]
3+303.4，[M+4H]
4+227.7，[M+5H]
5+182.4；calu[M+3H]
3+303.3，[M+4H]
4+227.8，[M+5H]
5+182.4
Embodiment 7
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:8); Theoretical relative molecular mass 999.1
ESI-MSm/z：found[M+3H]
3+334.0，[M+4H]
4+250.7，[M+5H]
5+200.9；calu[M+3H]
3+334.0，[M+4H]
4+250.8，[M+5H]
5+200.8
Embodiment 8
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-(D-Ala)-Ser (SEQ.ID NO:9); Theoretical relative molecular mass 985.1
ESI-MSm/z：found[M+3H]
3+329.5，[M+4H]
4+247.4，[M+5H]
5+198.0；calu[M+3H]
3+329.4，[M+4H]
4+247.3，[M+5H]
5+198.0
Embodiment 9
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Gly-Ser (SEQ.ID NO:10); Theoretical relative molecular mass 985.1
ESI-MSm/z：found[M+3H]
3+329.4，[M+4H]
4+247.5，[M+5H]
5+198.0；calu[M+3H]
3+329.4，[M+4H]
4+247.3，[M+5H]
5+198.0
Embodiment 10
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Cys-Ser (SEQ.ID NO:11); Theoretical relative molecular mass 1031.2
ESI-MSm/z：found[M+3H]
3+344.6，[M+4H]
4+258.8，[M+5H]
5+207.3；calu[M+3H]
3+344.7，[M+4H]
4+258.8，[M+5H]
5+207.2
Embodiment 11
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Met-Ser (SEQ.ID NO:12); Theoretical relative molecular mass 1059.2
ESI-MSm/z：found[M+3H]
3+354.1，[M+4H]
4+265.8，[M+5H]
5+212.7；calu[M+3H]
3+354.1，[M+4H]
4+265.8，[M+5H]
5+212.8
Embodiment 12
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Ser-Ser (SEQ.ID NO:13); Theoretical relative molecular mass 1015.1
ESI-MSm/z：found[M+3H]
3+339.5，[M+4H]
4+254.8，[M+5H]
5+204.1；calu[M+3H]
3+339.4，[M+4H]
4+254.8，[M+5H]
5+204.0
Embodiment 13
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Lys-Ser (SEQ.ID NO:14); Theoretical relative molecular mass 1059.2
ESI-MSm/z：found[M+3H]
3+353.2，[M+4H]
4+265.1，[M+5H]
5+212.3；calu[M+3H]
3+353.1，[M+4H]
4+265.1，[M+5H]
5+212.2
Embodiment 14
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:15); Theoretical relative molecular mass 909.0
ESI-MSm/z：found[M+3H]
3+304.1，[M+4H]
4+228.1，[M+5H]
5+183.0；calu[M+3H]
3+304.0，[M+4H]
4+228.2，[M+5H]
5+182.8
Embodiment 15
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Gly-Ser (SEQ.ID NO:16); Theoretical relative molecular mass 909.0
ESI-MSm/z：found[M+3H]
3+304.0，[M+4H]
4+228.3，[M+5H]
5+183.0；calu[M+3H]
3+304.0，[M+4H]
4+228.2，[M+5H]
5+182.8
Embodiment 16
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Cys-Ser (SEQ.ID NO:17); Theoretical relative molecular mass 955.1
ESI-MSm/z：found[M+3H]
3+319.2，[M+4H]
4+239.7，[M+5H]
5+192.0；calu[M+3H]
3+319.4，[M+4H]
4+239.8，[M+5H]
5+192.0
Embodiment 17
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Arg-Ser (SEQ.ID NO:18); Theoretical relative molecular mass 1008.1
ESI-MSm/z：found[M+3H]
3+337.1，[M+4H]
4+253.2，[M+5H]
5+202.7；calu[M+3H]
3+337.0，[M+4H]
4+253.0，[M+5H]
5+202.6
Embodiment 18
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Met-Ser (SEQ.ID NO:19); Theoretical relative molecular mass 983.1
ESI-MSm/z：found[M+3H]
3+328.7，[M+4H]
4+246.9，[M+5H]
5+197.8；calu[M+3H]
3+328.7，[M+4H]
4+246.8，[M+5H]
5+197.6
Embodiment 19
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Ser-Ser (SEQ.ID NO:20); Theoretical relative molecular mass 939.0
ESI-MSm/z：found[M+3H]
3+314.1，[M+4H]
4+235.9，[M+5H]
5+188.6；calu[M+3H]
3+314.0，[M+4H]
4+235.8，[M+5H]
5+188.8
Embodiment 20
(D-Ala)-Pro-Tyr-Tyr-Ser-Ile-Lys-Gly-Ser (SEQ.ID NO:21); Theoretical relative molecular mass 985.1
ESI-MSm/z：found[M+3H]
3+329.5，[M+4H]
4+247.4，[M+5H]
5+198.1；calu[M+3H]
3+329.4，[M+4H]
4+247.3，[M+5H]
5+198.0
Embodiment 21
(D-Ala)-Pro-Tyr-Tyr-Ser-Ile-Lys-Cys-Ser (SEQ.ID NO:22); Theoretical relative molecular mass 1031.2
ESI-MSm/z：found[M+3H]
3+344.8，[M+4H]
4+258.7，[M+5H]
5+207.1；calu[M+3H]
3+344.7，[M+4H]
4+258.8，[M+5H]
5+207.2
Embodiment 22
(D-Ala)-Pro-Tyr-Tyr-Ser-Ile-Lys-Met-Ser (SEQ.ID NO:23); Theoretical relative molecular mass 1059.2
ESI-MSm/z：found[M+3H]
3+354.0，[M+4H]
4+265.7，[M+5H]
5+212.8；calu[M+3H]
3+354.1，[M+4H]
4+265.8，[M+5H]
5+212.8
Embodiment 23
(D-Ala)-Pro-Tyr-Tyr-Ser-Ile-Lys-Ser-Ser (SEQ.ID NO:24); Theoretical relative molecular mass 1015.1
ESI-MSm/z：found[M+3H]
3+339.3，[M+4H]
4+254.7，[M+5H]
5+204.0；calu[M+3H]
3+339.4，[M+4H]
4+254.8，[M+5H]
5+204.0
Embodiment 24
(D-Ala)-Pro-Tyr-Tyr-Ser-Ile-Lys-Lys-Ser (SEQ.ID NO:25); Theoretical relative molecular mass 999.1
ESI-MSm/z：found[M+3H]
3+334.1，[M+4H]
4+250.9，[M+5H]
5+200.7；calu[M+3H]
3+334.0[M+4H]
4+250.8，[M+5H]
5+200.8
Embodiment 25
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:26); Theoretical relative molecular mass 909.0
ESI-MSm/z：found[M+3H]
3+304.1，[M+4H]
4+228.1，[M+5H]
5+182.7；calu[M+3H]
3+304.0[M+4H]
4+228.2，[M+5H]
5+182.8
Embodiment 26
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Gly-Ser (SEQ.ID NO:27); Theoretical relative molecular mass 909.0
ESI-MSm/z：found[M+3H]
3+304.2，[M+4H]
4+228.2，[M+5H]
5+182.6；calu[M+3H]
3+304.0[M+4H]
4+228.2，[M+5H]
5+182.8
Embodiment 27
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Cys-Ser (SEQ.ID NO:28); Theoretical relative molecular mass 955.1
ESI-MSm/z：found[M+3H]
3+319.5，[M+4H]
4+239.7，[M+5H]
5+192.1；calu[M+3H]
3+319.4[M+4H]
4+239.8，[M+5H]
5+192.0
Embodiment 28
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Arg-Ser (SEQ.ID NO:29); Theoretical relative molecular mass 1008.1
ESI-MSm/z：found[M+3H]
3+337.1，[M+4H]
4+253.2，[M+5H]
5+202.5，calu[M+3H]
3+337.0[M+4H]
4+253.0，[M+5H]
5+202.6
Embodiment 29
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Met-Ser (SEQ.ID NO:30); Theoretical relative molecular mass 939.0
ESI-MSm/z：found[M+3H]
3+314.2，[M+4H]
4+235.7，[M+5H]
5+188.9；calu[M+3H]
3+314.0[M+4H]
4+235.8，[M+5H]
5+188.8
Embodiment 30
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Ser-Ser (SEQ.ID NO:31); Theoretical relative molecular mass 939.0
ESI-MSm/z：found[M+3H]
3+314.2，[M+4H]
4+235.9，[M+5H]
5+188.8；calu[M+3H]
3+314.0[M+4H]
4+235.8，[M+5H]
5+188.8
Embodiment 31
Gly-Pro-Tyr-Tyr-Ser-Ile-Lys-Gly-Ser (SEQ.ID NO:32); Theoretical relative molecular mass 971.1
ESI-MSm/z：found[M+3H]
3+324.6，[M+4H]
4+243.9，[M+5H]
5+195.3；calu[M+3H]
3+324.7[M+4H]
4+243.8，[M+5H]
5+195.2
Embodiment 32
Gly-Pro-Tyr-Tyr-Ser-Ile-Lys-Cys-Ser (SEQ.ID NO:33); Theoretical relative molecular mass 1017.2
ESI-MSm/z：found[M+3H]
3+340.1，[M+4H]
4+255.3，[M+5H]
5+204.5；calu[M+3H]
3+340.1[M+4H]
4+255.3，[M+5H]
5+204.4
Embodiment 33
Gly-Pro-Tyr-Tyr-Ser-Ile-Lys-Met-Ser (SEQ.ID NO:34); Theoretical relative molecular mass 1045.2
ESI-MSm/z：found[M+3H]
3+349.5，[M+4H]
4+262.3，[M+5H]
5+210.1；calu[M+3H]
3+349.4[M+4H]
4+262.3，[M+5H]
5+210.0
Embodiment 34
Gly-Pro-Tyr-Tyr-Ser-Ile-Lys-Ser-Ser (SEQ.ID NO:35); Theoretical relative molecular mass 1001.1
ESI-MSm/z：found[M+3H]
3+334.7，[M+4H]
4+251.3，[M+5H]
5+201.1；calu[M+3H]
3+334.7[M+4H]
4+251.3，[M+5H]
5+201.2
Embodiment 35
Gly-Pro-Tyr-Tyr-Ser-Ile-Lys-Lys-Ser (SEQ.ID NO:36); Theoretical relative molecular mass 1042.2
ESI-MSm/z：found[M+3H]
3+348.5，[M+4H]
4+261.3，[M+5H]
5+209.3；calu[M+3H]
3+348.4[M+4H]
4+261.5，[M+5H]
5+209.4
Embodiment 36
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:37); Theoretical relative molecular mass 909.0
ESI-MSm/z：found[M+3H]
3+304.1，[M+4H]
4+228.3，[M+5H]
5+182.7；calu[M+3H]
3+304.0[M+4H]
4+228.2，[M+5H]
5+182.8
Embodiment 37
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Gly-Ser (SEQ.ID NO:38); Theoretical relative molecular mass 895.0
ESI-MSm/z：found[M+3H]
3+299.1，[M+4H]
4+224.8，[M+5H]
5+180.0；calu[M+3H]
3+299.3[M+4H]
4+224.7，[M+5H]
5+180.0
Embodiment 38
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Cys-Ser (SEQ.ID NO:39); Theoretical relative molecular mass 941.1
ESI-MSm/z：found[M+3H]
3+314.6，[M+4H]
4+236.4，[M+5H]
5+189.1；calu[M+3H]
3+314.7[M+4H]
4+236.3，[M+5H]
5+189.2
Embodiment 39
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Arg-Ser (SEQ.ID NO:40); Theoretical relative molecular mass 941.1
ESI-MSm/z：found[M+3H]
3+332.5，[M+4H]
4+249.4，[M+5H]
5+199.8；calu[M+3H]
3+332.4[M+4H]
4+249.5，[M+5H]
5+199.8
Embodiment 40
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Met-Ser (SEQ.ID NO:41); Theoretical relative molecular mass 941.1
ESI-MSm/z：found[M+3H]
3+332.3，[M+4H]
4+249.5，[M+5H]
5+199.9；calu[M+3H]
3+332.4[M+4H]
4+249.5，[M+5H]
5+199.8
Embodiment 41
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Ser-Ser (SEQ.ID NO:42); Theoretical relative molecular mass 925.0
ESI-MSm/z：found[M+3H]
3+309.3，[M+4H]
4+232.3，[M+5H]
5+186.1；calu[M+3H]
3+309.3[M+4H]
4+232.2，[M+5H]
5+186.0
Embodiment 42
Ala-Pro-Ala-(D-Ala)-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:43); Theoretical relative molecular mass 814.9
ESI-MSm/z：found[M+3H]
3+272.7，[M+4H]
4+204.6，[M+5H]
5+164.1；calu[M+3H]
3+272.6[M+4H]
4+204.7，[M+5H]
5+164.0
Embodiment 43
Ala-Pro-Ala-Arg-Tyr-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:44); Theoretical relative molecular mass 900.0
ESI-MSm/z：found[M+3H]
3+301.1，[M+4H]
4+226.2，[M+5H]
5+181.1；calu[M+3H]
3+301.0[M+4H]
4+226.0，[M+5H]
5+181.0
Embodiment 44
Ala-Pro-(D-Ala)-Cys-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:45); Theoretical relative molecular mass 1063.2
ESI-MSm/z：found[M+3H]
3+355.2，[M+4H]
4+266.7，[M+5H]
5+213.8；calu[M+3H]
3+355.4[M+4H]
4+266.8，[M+5H]
5+213.6
Embodiment 45
Ala-Pro-(D-Ala)-Gly-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:46); Theoretical relative molecular mass 800.9
ESI-MSm/z：found[M+3H]
3+268.1，[M+4H]
4+201.3，[M+5H]
5+161.2；calu[M+3H]
3+268.0[M+4H]
4+201.2，[M+5H]
5+161.2
Embodiment 46
Ala-Pro-(D-Ala)-His-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:47); Theoretical relative molecular mass 881.0
ESI-MSm/z：found[M+3H]
3+294.6，[M+4H]
4+221.3，[M+5H]
5+177.2；calu[M+3H]
3+294.7[M+4H]
4+221.2，[M+5H]
5+177.2
Embodiment 47
Ala-Pro-(D-Ala)-Lys-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:48); Theoretical relative molecular mass 872.0
ESI-MSm/z：found[M+3H]
3+291.6，[M+4H]
4+219.1，[M+5H]
5+175.5；calu[M+3H]
3+294.7[M+4H]
4+219.0，[M+5H]
5+175.4
Embodiment 48
Ala-Pro-(D-Ala)-Tyr-Ser-Ile-Lys-Ala-Ser (SEQ.ID NO:49); Theoretical relative molecular mass 907.0
ESI-MSm/z：found[M+3H]
3+303.3，[M+4H]
4+227.9，[M+5H]
5+182.5；calu[M+3H]
3+303.3[M+4H]
4+227.8，[M+5H]
5+182.4
Embodiment 49
Gly-Pro-Ala-Tyr-Ser-Ile-Lys-Gly-Ser (SEQ.ID NO:50); Theoretical relative molecular mass 879.0
ESI-MSm/z：found[M+3H]
3+294.1，[M+4H]
4+220.6，[M+5H]
5+176.8；calu[M+3H]
3+294.0[M+4H]
4+220.7，[M+5H]
5+176.8
Embodiment 50
Hypoglycemic activity experiment in MC-JJ0107 and the similar object thereof
Get 10 the week age male mouse of kunming (body weight 18～22g), random packet, 6 every group.Tail vein injection tetraoxypyrimidine administration modeling, dosage is 60mg/kg, after 72 hours, mouse fasting 5～6 hours is surveyed blood sugar and is selected the blood glucose value scope 13～23 mouse random packet, 6 every group.Mouse 1mg/kg successive administration 10d abdominal injection MC-JJ0107 polypeptide and analogue thereof behind the Cheng Mo.0,30,60,90,120 usefulness blood glucose meter are measured blood glucose value.
As shown in table 1, the hypoglycemic activity of MC-JJ0107 polypeptide and analogue thereof is better than N1,N1-Dimethylbiguanide.
Table 1MC-JJ0107 and the hypoglycemic effect of analogue thereof
| ??0min | ??30min | ??60min | ??90min | ??120min | |
| Negative blank | ??4.60±2.38 | ??4.68±2.36 | ??4.62±1.94 | ??4.46±2.02 | ??4.12±1.64 |
| Positive blank | ??25.32±1.77 | ??22.78±2.26 | ??21.68±2.82 | ??19.16±1.00 | ??17.58±2.08 |
| N1,N1-Dimethylbiguanide | ??23.15±11.48 | ??20.45±5.97 | ??18.03±6.24* | ??16.01±3.84* | ??14.23±5.77* |
| ??0min | ??30min | ??60min | ??90min | ??120min | |
| ??SEQ.ID?NO：3 | ??16.56±7.65** | ??14.64±3.33*** | ??13.42±6.79*** | ??11.26±3.77*** | ??9.21±4.55** |
| ??SEQ.ID?NO：5 | ??17.15±3.22** | ??16.34±6.05** | ??15.34±5.60** | ??14.52±8.75** | ??12.48±4.20* |
| ??SEQ.ID?NO：7 | ??19.67±11.57* | ??17.77±7.73 | ??15.27±6.00** | ??13.11±4.26*** | ??12.81±7.51** |
| ??SEQ.ID?NO：8 | ??21.35±5.09* | ??19.42±4.27* | ??16.20±5.30** | ??13.80±6.83*** | ??12.38±7.88** |
| ??SEQ.ID?NO：9 | ??20.88±5.93* | ??18.25±1.97* | ??17.68±4.54* | ??16.18±7.55* | ??12.71±4.54** |
| ??SEQ.ID?NO：14 | ??18.47±4.02** | ??16.65±4.05** | ??16.55±7.65* | ??14.9±3.72** | ??11.67±8.21** |
| ??SEQ.ID?NO：19 | ??17.36±7.16** | ??15.81±4.18** | ??14.93±3.38*** | ??13.91±2.36** | ??10.98±6.11*** |
| ??SEQ.ID?NO：25 | ??20.44±3.04* | ??18.78±1.34* | ??16.84±3.02* | ??14.54±3.24** | ??14.66±3.05* |
| ??SEQ.ID?NO：31 | ??22.28±1.60* | ??16.51±2.23** | ??13.65±4.32*** | ??11.43±2.41*** | ??8.23±2.45*** |
| ??SEQ.ID?NO：42 | ??17.18±0.92** | ??16.10±1.64** | ??15.88±2.95* | ??14.67±4.36** | ??13.82±3.11* |
n＝6，
*P＜0.05，**P＜0.01，***P＜0.001?vs?saline
Sequence table
＜110〉China Medicine University
＜120〉microwave promotes solid phase synthesis balsam pear MC-JJ0107 polypeptide analog and application thereof
<160>91
<210>1
<211>9
<212>PRT
＜213〉artificial sequence
<220>
＜221〉synthetic construct
<222>(1)..(1)
＜223〉the 1st Xaa is Ala, D-Ala, Gly or Ser
<220>
＜221〉synthetic construct
<222>(3)..(3)
＜223〉the 3rd Xaa is Ala, D-Ala, Arg, Cys, Gly, His, Lys, Met, Tyr or Ser
<220>
＜221〉synthetic construct
<222>(4)..(4)
＜223〉the 4th Xaa is Ala, D-Ala, Gly, Lys, Tyr or Ser
<220>
＜221〉synthetic construct
<222>(7)..(7)
＜223〉the 7th Xaa is Lys or Ser
<220>
＜221〉synthetic construct
<222>(8)..(8)
＜223〉the 8th Xaa is Ala, D-Ala, Gly, Cys, Arg, Lys, Met or Ser
<400>1
Xaa1-Pro-Xaa2-Xaa3-Ser-Ile-Xaa4-Xaa5-Ser
1???????????????????5
<210>2
<211>10
<212>PRT
＜213〉artificial sequence
<400>2
Ala-Pro-Ala-Ala-Ser-Ile-Lys-Ala-Ser
1????????????????5
<210>3
<211>10
<212>PRT
＜213〉artificial sequence
<400>3
Ala-Pro-Ala-Cys-Ser-Ile-Lys-Ala-Ser
1????????????????5
<210>4
<211>10
<212>PRT
＜213〉artificial sequence
<400>4
Ala-Pro-Ala-Gly-Ser-Ile-Lys-Ala-Ser
1????????????????5
<210>5
<211>10
<212>PRT
＜213〉artificial sequence
<400>5
Ala-Pro-Ala-His-Ser-Ile-Lys-Ala-Ser
1????????????????5
<210>6
<211>10
<212>PRT
＜213〉artificial sequence
<400>6
Ala-Pro-Ala-Lys-Ser-Ile-Lys-Ala-Ser
1????????????????5
<210>7
<211>10
<212>PRT
＜213〉artificial sequence
<400>7
Ala-Pro-Ala-Tyr-Ser-Ile-Lys-Ala-Ser
1????????????????5
<210>8
<211>10
<212>PRT
＜213〉artificial sequence
<400>8
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Ala-Ser
1????????????????5
<210>9
<211>10
<212>PRT
＜213〉artificial sequence
<400>9
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-(D-Ala)-Ser
1????????????????5
<210>10
<211>10
<212>PRT
＜213〉artificial sequence
<400>10
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Gly-Ser
1????????????????5
<210>11
<211>10
<212>PRT
＜213〉artificial sequence
<400>11
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Cys-Ser
1?????????????????5
<210>12
<211>10
<212>PRT
＜213〉artificial sequence
<400>12
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Met-Ser
1????????????????5
<210>13
<211>10
<212>PRT
＜213〉artificial sequence
<400>13
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Ser-Ser
1?????????????????5
<210>14
<211>10
<212>PRT
＜213〉artificial sequence
<400>14
Ala-Pro-Tyr-Tyr-Ser-Ile-Lys-Lys-Ser
1????????????????5
<210>15
<211>10
<212>PRT
＜213〉artificial sequence
<400>15
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Ala-Ser
1???????????????5
<210>16
<211>10
<212>PRT
＜213〉artificial sequence
<400>16
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Gly-Ser
1???????????????5
<210>17
<211>10
<212>PRT
＜213〉artificial sequence
<400>17
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Cys-Ser
1?????????????????5
<210>18
<211>10
<212>PRT
＜213〉artificial sequence
<400>18
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Arg-Ser
1???????????????5
<210>19
<211>10
<212>PRT
＜213〉artificial sequence
<400>19
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Met-Ser
1?????????????????5
<210>20
<211>10
<212>PRT
＜213〉artificial sequence
<400>20
Ala-Pro-Ser-Tyr-Ser-Ile-Lys-Ser-Ser
1????????????????5
<210>21
<211>10
<212>PRT
＜213〉artificial sequence
<400>21
(D-Ala)-Pro-Tyr-Tyr-Ser-Ile-Lys-Gly-Ser
1????????????????????5
<210>22
<211>10
<212>PRT
＜213〉artificial sequence
<400>22
(D-Ala)-Pro-Tyr-Tyr-Ser-Ile-Lys-Cys-Ser
1????????????????????5
<210>23
<211>10
<212>PRT
＜213〉artificial sequence
<400>23
(D-Ala)-Pro-Tyr-Tyr-Ser-Ile-Lys-Met-Ser
1????????????????????5
<210>24
<211>10
<212>PRT
＜213〉artificial sequence
<400>24
(D-Ala)-Pro-Tyr-Tyr-Ser-Ile-Lys-Ser-Ser
1????????????????????5
<210>25
<211>10
<212>PRT
＜213〉artificial sequence
<400>25
(D-Ala)-Pro-Tyr-Tyr-Ser-Ile-Lys-Lys-Ser
1????????????????????5
<210>26
<211>10
<212>PRT
＜213〉artificial sequence
<400>26
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Ala-Ser
1????????????????????5
<210>27
<211>10
<212>PRT
＜213〉artificial sequence
<400>27
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Gly-Ser
1????????????????????5
<210>28
<211>10
<212>PRT
＜213〉artificial sequence
<400>28
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Cys-Ser
1????????????????????5
<210>29
<211>10
<212>PRT
＜213〉artificial sequence
<400>29
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Arg-Ser
1????????????????????5
<210>30
<211>10
<212>PRT
＜213〉artificial sequence
<400>30
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Met-Ser
1????????????????????5
<210>31
<211>10
<212>PRT
＜213〉artificial sequence
<400>31
(D-Ala)-Pro-Ser-Tyr-Ser-Ile-Lys-Ser-Ser
1????????????????????5
<210>32
<211>10
<212>PRT
＜213〉artificial sequence
<400>32
Gly-Pro-Tyr-Tyr-Ser-Ile-Lys-Gly-Ser
1????????????????5
<210>33
<211>10
<212>PRT
＜213〉artificial sequence
<400>33
Gly-Pro-Tyr-Tyr-Ser-Ile-Lys-Cys-Ser
1????????????????5
<210>34
<211>10
<212>PRT
＜213〉artificial sequence
<400>34
Gly-Pro-Tyr-Tyr-Ser-Ile-Lys-Met-Ser
1????????????????5
<210>35
<211>10
<212>PRT
＜213〉artificial sequence
<400>35
Gly-Pro-Tyr-Tyr-Ser-Ile-Lys-Ser-Ser
1????????????????5
<210>36
<211>10
<212>PRT
＜213〉artificial sequence
<400>36
Gly-Pro-Tyr-Tyr-Ser-Ile-Lys-Lys-Ser
1????????????????5
<210>37
<211>10
<212>PRT
＜213〉artificial sequence
<400>37
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Ala-Ser
1????????????????5
<210>38
<211>10
<212>PRT
＜213〉artificial sequence
<400>38
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Gly-Ser
1?????????????????5
<210>39
<211>10
<212>PRT
＜213〉artificial sequence
<400>39
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Cys-Ser
1?????????????????5
<210>40
<211>10
<212>PRT
＜213〉artificial sequence
<400>40
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Arg-Ser
1???????????????5
<210>41
<211>10
<212>PRT
＜213〉artificial sequence
<400>41
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Met-Ser
1?????????????????5
<210>42
<211>10
<212>PRT
＜213〉artificial sequence
<400>42
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Ser-Ser
1?????????????????5
<210>43
<211>10
<212>PRT
＜213〉artificial sequence
<400>43
Ala-Pro-Ala-(D-Ala)-Ser-Ile-Lys-Ala-Ser
1???????????????????5
<210>44
<211>10
<212>PRT
＜213〉artificial sequence
<400>44
Ala-Pro-Ala-Arg-Tyr-Ser-Ile-Lys-Ala-Ser
1????????????????5??????????????????10
<210>45
<211>10
<212>PRT
＜213〉artificial sequence
<400>45
Ala-Pro-(D-Ala)-Cys-Ser-Ile-Lys-Ala-Ser
1????????????????????5
<210>46
<211>10
<212>PRT
＜213〉artificial sequence
<400>46
Ala-Pro-(D-Ala)-Gly-Ser-Ile-Lys-Ala-Ser
1???????????????????5
<210>47
<211>10
<212>PRT
＜213〉artificial sequence
<400>47
Ala-Pro-(D-Ala)-His-Ser-Ile-Lys-Ala-Ser
1????????????????????5
<210>48
<211>10
<212>PRT
＜213〉artificial sequence
<400>48
Ala-Pro-(D-Ala)-Lys-Ser-Ile-Lys-Ala-Ser
1????????????????????5
<210>49
<211>10
<212>PRT
＜213〉artificial sequence
<400>49
Ala-Pro-(D-Ala)-Tyr-Ser-Ile-Lys-Ala-Ser
1????????????????????5
<210>50
<211>10
<212>PRT
＜213〉artificial sequence
<400>50
Gly-Pro-Ala-Tyr-Ser-Ile-Lys-Gly-Ser
1????????????????5
<210>51
<211>10
<212>PRT
＜213〉artificial sequence
<400>51
Gly-Pro-Ala-Tyr-Ser-Ile-Lys-Cys-Ser
1????????????????5
<210>52
<211>10
<212>PRT
＜213〉artificial sequence
<400>52
Gly-Pro-Ala-Tyr-Ser-Ile-Lys-Met-Ser
1????????????????5
<210>53
<211>10
<212>PRT
＜213〉artificial sequence
<400>53
Gly-Pro-Ala-Tyr-Ser-Ile-Lys-Ser-Ser
1????????????????5
<210>54
<211>10
<212>PRT
＜213〉artificial sequence
<400>54
Gly-Pro-Ala-Tyr-Ser-Ile-Lys-Lys-Ser
1????????????????5
<210>55
<211>10
<212>PRT
＜213〉artificial sequence
<400>55
Gly-Pro-Ala-Tyr-Ser-Ile-Lys-Ala-Ser
1????????????????5
<210>56
<211>10
<212>PRT
＜213〉artificial sequence
<400>56
Gly-Pro-Ala-Tyr-Ser-Ile-Lys-Gly-Ser
1????????????????5
<210>57
<211>10
<212>PRT
＜213〉artificial sequence
<400>57
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Cys-Ser
1????????????????5
<210>58
<211>10
<212>PRT
＜213〉artificial sequence
<400>58
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Arg-Ser
1???????????????5
<210>59
<211>10
<212>PRT
＜213〉artificial sequence
<400>59
Gly-Pro-Ser-Tyr-Ser-Ile-Lys-Met-Ser
1????????????????5
<210>60
<211>10
<212>PRT
＜213〉artificial sequence
<400>60
Gly-Pro-Ser-Tyr-Ser-le-Lys-Ser-Ser
1????????????????5
Claims (8)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010177944A CN101824074A (en) | 2010-05-20 | 2010-05-20 | Micro-assisted solid-phase synthesis of analogue of MC-JJ0107 polypeptide isolated from Momordica charantia and application of the analogue |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010177944A CN101824074A (en) | 2010-05-20 | 2010-05-20 | Micro-assisted solid-phase synthesis of analogue of MC-JJ0107 polypeptide isolated from Momordica charantia and application of the analogue |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101824074A true CN101824074A (en) | 2010-09-08 |
Family
ID=42688259
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010177944A Withdrawn CN101824074A (en) | 2010-05-20 | 2010-05-20 | Micro-assisted solid-phase synthesis of analogue of MC-JJ0107 polypeptide isolated from Momordica charantia and application of the analogue |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101824074A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1255044A (en) * | 1997-04-01 | 2000-05-31 | 卡里克斯治疗公司 | Orally active fraction of momordica charantia, active peptides thereof, and their use for treating diabetes |
| CN1418890A (en) * | 2002-09-23 | 2003-05-21 | 北海海玉农业开发有限责任公司 | Process for preparing momordic glucose-reducing polypeptide |
-
2010
- 2010-05-20 CN CN201010177944A patent/CN101824074A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1255044A (en) * | 1997-04-01 | 2000-05-31 | 卡里克斯治疗公司 | Orally active fraction of momordica charantia, active peptides thereof, and their use for treating diabetes |
| CN1418890A (en) * | 2002-09-23 | 2003-05-21 | 北海海玉农业开发有限责任公司 | Process for preparing momordic glucose-reducing polypeptide |
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Open date: 20100908 |