CN107857809A - A kind of new method of synthesis in solid state Thymosin alpha 1 - Google Patents
A kind of new method of synthesis in solid state Thymosin alpha 1 Download PDFInfo
- Publication number
- CN107857809A CN107857809A CN201711321988.1A CN201711321988A CN107857809A CN 107857809 A CN107857809 A CN 107857809A CN 201711321988 A CN201711321988 A CN 201711321988A CN 107857809 A CN107857809 A CN 107857809A
- Authority
- CN
- China
- Prior art keywords
- thymosin alpha
- otbu
- glu
- synthesis
- val
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/57581—Thymosin; Related peptides
Abstract
The invention discloses a kind of new method of synthesis in solid state Thymosin alpha 1, comprise the following steps：The synthesis of the resin of Thymosin alpha 1 precursor peptide I, the synthesis of the resin of Thymosin alpha 1 precursor peptide II, the synthesis of the thick peptide III of Thymosin alpha 1 and the synthesis of Thymosin alpha 1；Utilize Fmoc synthesis in solid state principles, develop solid phase and efficiently synthesize technology, using it is common be easy to get, low cost source chemicals come synthetically prepared, pass through process optimization and distinctive microwave reaction technical finesse, Thymosin alpha 1 crude yield is up to 85%, its sterling yield reaches 60%, substantially increases the yield of Thymosin alpha 1；The preparation method is simple to operate, and synthesis cycle is short, and production cost is low, and accessory substance is few, and product yield is high, beneficial to rapidly mass producing.
Description
Technical field
Originally polypeptide drugs preparing technical field is belonged to, more particularly to a kind of new method of synthesis in solid state Thymosin alpha 1.
Background technology
Chinese：Thymosin alpha 1；
English name：Thymosinα1；
Structural formula is：
Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-
Lys-G lu-Lys-Lys-Glu-Val-Val-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH；
Molecular formula：C129H215N33O55；
Molecular weight：3108.37
Thymosin alpha 1 (Thymosin α 1) is a kind of medicine treated chronic hepatitis B and strengthen immune system response
Peptide.Thymosin alpha 1 promotes the maturation of T lymphocytes by stimulating peripheral blood lymphocyte mitogen, increases antigen or mitogen
The lymphokine such as interferon-' alpha ', interferon gamma and the interleukin-22 of T cell secretion, interleukin-13 is horizontal after original activation, increases simultaneously
T cell surface lymphokine receptor is horizontal.It can also strengthen allosome by the activation to cd4 cell and the autologous mankind mix leaching
Bar cell effect.The aggregation of NK cells before Thymosin alpha 1 may increase, and interferon can strengthen its cytotoxicity.In vivo studies
It has been shown that, Thymosin alpha 1 can improve the expression of the mouse lymphocyte IL-2R after concanavalin A activates, simultaneously
Improve the secretion level of interleukin-22.
Thymosin alpha 1 synthesis preparation method in the market, synthesis cycle length, production cost is high, is unfavorable for bivalirudin
Large-scale production.
The content of the invention
It is an object of the invention to provide a kind of new method of synthesis in solid state Thymosin alpha 1, the preparation method reaction condition temperature
It is high with, reaction efficiency, cost is low, has the wide application prospect of production Thymosin alpha 1.
The purpose of the present invention can be achieved through the following technical solutions：
A kind of new method of synthesis in solid state Thymosin alpha 1, comprises the following steps：
S1, Thymosin alpha 1 I-resin of precursor peptide synthesis：
Using resin as carrier, pass through solid-phase synthesis, addition protection acid, condensing agent and activator to Peptide systhesis reactor
In, the amino acid in Thymosin alpha 1 sequence is activated successively, is condensed, microwave reaction, deprotection reaction and washing, is connected successively
The amino acid in Thymosin alpha 1 sequence is connect, that is, obtains following Thymosin alpha 1 I-resin of precursor peptide：
Fmoc-Ser(tBu)-Asp(OtBu)-Ala-Ala-Val-Asp(OtBu)-Thr(tBu)-Ser(tBu)-Ser
(tBu)-Glu(OtBu)-Ile-Thr(tBu)-Thr(tBu)-Lys(Boc)-Asp(OtBu)-Leu-Lys(Boc)-Glu
(OtBu)-L ys(Boc)-Lys(Boc)-Glu(OtBu)-Val-Val-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu
(OtBu)-Ala-Glu (OtBu)-Asn (trt)-resin；
S2, Thymosin alpha 1 II-resin of precursor peptide synthesis：
Acetylation reagent is added into Thymosin alpha 1 I-resin of precursor peptide and carries out the reaction of N-terminal acetylation end socket, is obtained as follows
Thymosin alpha 1 II-resin of precursor peptide：
Ac-Ser(tBu)-Asp(OtBu)-Ala-Ala-Val-Asp(OtBu)-Thr(tBu)-Ser(tBu)-Ser
(tBu)-G lu(OtBu)-Ile-Thr(tBu)-Thr(tBu)-Lys(Boc)-Asp(OtBu)-Leu-Lys(Boc)-Glu
(OtBu)-Lys(Boc)-Lys(Boc)-Glu(OtBu)-Val-Val-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu
(OtBu)-Ala-G lu (OtBu)-Asn (trt)-resin；
The synthesis of the thick peptide III of S3, Thymosin alpha 1：
Cutting reagent is added into Thymosin alpha 1 II-resin of precursor peptide and carries out cleavage reaction, then settles, has obtained thymus gland
The thick peptides III of peptide α 1；
S4, Thymosin alpha 1 synthesis：
The thick peptide III of Thymosin alpha 1 is purified and lyophilized purify lyophilized is to obtain following Thymosin alpha 1：
Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-
Lys-G lu-Lys-Lys-Glu-Val-Val-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH。
Further, the resin described in step S1 is Wang Resin resins, and the substitution value of Wang Resin resins is
0.45mmol/g, described condensing agent and activator are HBTU/DIEA.
Further, the protection acid described in step S1 is Fmoc- protection acid, and the Fmoc- protected amino acids of condensation include
Fmoc-Asn(trt)-OH、Fmoc-Glu(Otbu)-OH、Fmoc-Ala-OH、Fmoc-Val-OH、Fmoc-Lys(Boc)-OH、
Fmoc-Leu-OH, Fmoc-Asp (Otbu)-OH, Fmoc-Thr (tbu)-OH, Fmoc-Ile-OH and Fmoc-Ser (tbu)-OH,
Amino acid and resin inventory are 1.5 in the condensation reaction:1, described setting-up point is 25 DEG C, condensation reaction time
For 20-30min.
Further, the microwave reaction time described in step S1 is 20s-25s.
Further, the deprotection reaction described in step S1 is deprotection agent from 20%Pip/DMF, and deprotection agent adds
Enter 1/3~1/2 that amount is Peptide systhesis reactor volume.
Further, the acetylation reagent described in step S2 is that volume ratio is aceticanhydride：DIEA：DMF=1:1:4 mixing
Liquid, acetylization reaction time are 20-30min.
Further, the cutting reagent described in step S3 is that volume ratio is TFA：Water=95:5 mixed liquor, cutting reagent
Addition be Peptide systhesis reactor volume 1/3~1/2, cleavage reaction temperature be 25 DEG C, described is settled into -20 DEG C of use
The absolute ether of low temperature precooling carries out the sedimentation of the thick peptide III of Thymosin alpha 1.
Further, the purifying described in step S4 prepares purifying using reversed-phased high performace liquid chromatographic.
Further, the condition of described reversed-phased high performace liquid chromatographic preparation purifying is：Chromatographic column is 10um from particle diameter
C18 prepare post, with A phases：0.1% acetic acid aqueous solution, B phases：0.1% acetic acid acetonitrile solution is mobile phase, according to following ladder
Spend the separating-purifying that program carries out polypeptide：
Beneficial effects of the present invention：
The present invention utilize Fmoc synthesis in solid state principles, develops solid phase and efficiently synthesizes technology, using it is common be easy to get, it is inexpensive
Source chemicals come it is synthetically prepared, pass through process optimization and distinctive microwave reaction technical finesse, Thymosin alpha 1 crude yield
Up to 85%, its sterling yield reaches 60%, substantially increases the yield of Thymosin alpha 1；Purifying replaces conventional three from acetic acid
Fluoroacetic acid is mobile phase, greatly reduces the content of trifluoroacetate in sterling, thoroughly removes trifluoroacetic acid to organism
Toxicity；The preparation method is simple to operate, and synthesis cycle is short, and production cost is low, and accessory substance is few, and product yield is high, beneficial to rapidly
Large-scale production.
Embodiment
The technical scheme in the embodiment of the present invention will be clearly and completely described below, it is clear that described implementation
Example only part of the embodiment of the present invention, rather than whole embodiments.It is common based on the embodiment in the present invention, this area
All other embodiment that technical staff is obtained under the premise of creative work is not made, belong to the model that the present invention protects
Enclose.
Embodiment 1
1st, the swelling of resin
Wang Resin (Wang resin) 0.2g that substitution value is 0.45mmol/g is weighed, is added from openend to Peptide systhesis
In reactor, take DCM reagents to add into reactor, resin is completely submerged in DCM solvents, fully contacted with solvent, it is molten
Swollen 2h；
2nd, the synthesis of I-resin of Thymosin alpha 1 precursor peptide
Thymosin alpha 1 I-resin of precursor peptide is as follows：
Fmoc-Ser(tBu)-Asp(OtBu)-Ala-Ala-Val-Asp(OtBu)-Thr(tBu)-Ser(tBu)-Ser
(tBu)-Glu(OtBu)-Ile-Thr(tBu)-Thr(tBu)-Lys(Boc)-Asp(OtBu)-Leu-Lys(Boc)-Glu
(OtBu)-L ys(Boc)-Lys(Boc)-Glu(OtBu)-Val-Val-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu
(OtBu)-Ala-Glu (OtBu)-Asn (trt)-resin；
(1), the activation of protected amino acid
The protection acid used starts at the corresponding protection acid of the 1st~31 amino acid and molecular weight such as table 1 below from resin end
It is shown, by taking the condensation of Fmoc-Asn (trt)-Wang resins as an example, 52mg Fmoc- are weighed according to the theoretical acid inventory of calculating
Asn (trt)-OH and 40mg HBTU add 2ml DMF and dissolved, then take 10ul DIEA to add with liquid-transfering gun in centrifuge tube
Enter into centrifuge tube, the well mixed protection acid solution activated；
(2), the deprotection and washing of resin
The protection acid solution of activation is taken to carry out ninhydrin color developing detection, if anti-without color reaction, amino acid protection activation
Should be complete, the solvent in Peptide systhesis reactor is drained with vavuum pump, is then added to the protection acid solution of above-mentioned activation more
In peptide symthesis reactor, then it is concussion reaction 30min in 25 DEG C of isothermal vibration device that Peptide systhesis reactor is placed in into temperature, shake
0.5ml DIEA are added after swinging, Peptide systhesis reactor is then placed in microwave reaction 25s in microwave chemical reactor, reacted
Bi Hou, the 20%Pip/DMF deprotection solution of 1/2 reactor volume is added into Peptide systhesis reactor, is placed in 30r/min's
Reaction 1min is rocked on decolorization swinging table can take off protective agent base Asn, be added after the solvent in reactor is drained with vavuum pump
DMF repeated washings 3 times, finally drain cleaning solvent again；
Using above-mentioned same method, the 2nd~31 Fmoc- protected amino acid is condensed successively, finally takes off Ser protection groups i.e.
Obtain Thymosin alpha 1 I-resin of precursor peptide；
The corresponding protection acid of the 1st~31 amino acid is started at from resin end and molecular weight is as shown in table 1 below：
Table 1
The conventional abbreviation of some in the present invention has following meanings：
Fmoc:Fluorenes methoxy carbonyl
DMF:N,N-dimethylformamide
Pip:Hexahydropyridine
TFA:Trifluoracetic acid
tBu:The tert-butyl group
Otbu：The oxygen tert-butyl group
Trt：Trityl
Boc：Tertbutyloxycarbonyl
DIC:N, N- Diisopropylcarbodiimide
DIEA:N, N- diisopropylethylamine
HOBt:I-hydroxybenzotriazole
HBTU：2- (1H- BTAs)-N, N, N', N'- tetramethylurea hexafluorophosphates；
3rd, the synthesis of II-resin of Thymosin alpha 1 precursor peptide
After step 2 obtains Thymosin alpha 1 I-resin of precursor peptide, the solvent in Peptide systhesis reactor is drained with vavuum pump；
The configuration of acetylation reagent：Aceticanhydride by volume：DIEA：DMF=1:1:4 configurations, it is that Peptide systhesis is anti-by volume
Answer the acetylation reagent of device 1/3~1/2 to be added thereto carry out acetylization reaction, reaction time 30min, that is, obtain Thymosin alpha 1
II-resin of precursor peptide；
4th, the synthesis of the thick peptide III of Thymosin alpha 1
After step 3 obtains Thymosin alpha 1 II-resin of precursor peptide, drained with vavuum pump molten in Peptide systhesis reactor
Agent；
The configuration of cutting reagent：TFA by volume：Water=95:5, it is well mixed, is Peptide systhesis reactor 1/ by volume
3 cutting reagent, which is added in Peptide systhesis reactor, carries out cleavage reaction, and reaction temperature is 25 DEG C, low by -20 DEG C after reaction
The absolute ether of warm precooling is added to the sedimentation that polypeptide crude product is carried out in Peptide systhesis reactor, that is, obtains the thick peptide of Thymosin alpha 1
Ⅲ；The thick peptide III of Thymosin alpha 1 after cutting sedimentation is in latex state, wherein containing more tfa salt and cutting reagent, is then adopted
Desalination is carried out with C18 chromatographic columns, to calculate crude product yield；The thick peptide III of Thymosin alpha 1 is dissolved and filtered, using mobile phase：A：
0.1% acetic acid aqueous solution, B：0.1% acetic acid acetonitrile solution, analyzed in the case where wavelength is 214nm according to following program sample introduction：
The thick peptide III of Thymosin alpha 1 after freezing is weighed, quality 72mg, it is 85.8% to be computed crude yield, than existing skill
Art only 60-70% yield is improved largely；
5th, the preparation of Thymosin alpha 1
The thick peptide III of Thymosin alpha 1 is dissolved and filtered, is prepared and purified using reversed-phased high performace liquid chromatographic, preparation condition is：
Chromatographic column prepares post from the C18 that particle diameter is 10um, with A phases：0.1% acetic acid aqueous solution, B phases：0.1% acetic acid acetonitrile solution is
Mobile phase, the separating-purifying of polypeptide is carried out according to following Gradient program：
Collection purification liquid is lyophilized to produce Thymosin alpha 1, obtains Thymosin alpha 1 sterling 34.2mg through weighing, purity reaches
99.5%, sterling yield is 61.2%.
Embodiment 2
The contrast experiment of Thymosin alpha 1 preparation method：
According to being washed after the normal 20~30min of condensation reaction of prior art, the yield of obtained Thymosin alpha 1 crude product is
68.7%, the purified Thymosin alpha 1 sterling that is prepared is 22.1mg, and sterling yield is 49.8%；
And the yield of the Thymosin alpha 1 obtained in embodiment 1 through microwave reaction technical finesse is 85.8%, it can be seen that change
The yield of technique Thymosin alpha 1 after entering is greatly enhanced.
Embodiment 3
To determine the stability of experimental result, the experiment of prior art and improved method synthesis Thymosin alpha 1 is repeated：
Being washed after the normal 20~30min of condensation reaction of prior art, the yield of obtained Thymosin alpha 1 crude product is 69.1%,
The purified Thymosin alpha 1 sterling that is prepared is 24.3mg, and sterling yield is 51.4%；
Using improved method：After 20~25min of normal condensation reaction, add 0.5ml DIEA, washed after microwave resin 25s,
The purity of Thymosin alpha 1 crude product is obtained up to 76%, crude yield 86.4%, the purified Thymosin alpha 1 sterling that is prepared is
36.3mg, sterling yield 61.7%；Confirm the correctness and stability of experimental data of the present invention；
Tested through above-described embodiment 2 and example 3, draw after normal synthesis further microwave reaction, be prepared
The yield of Thymosin alpha 1 sterling is higher, and effect is preferable.
Above content is only to design example and explanation of the invention, affiliated those skilled in the art
Various modifications or supplement are made to described specific embodiment or is substituted using similar mode, without departing from invention
Design or surmount scope defined in the claims, protection scope of the present invention all should be belonged to.
Claims (9)
- A kind of 1. new method of synthesis in solid state Thymosin alpha 1, it is characterised in that：Comprise the following steps：S1, Thymosin alpha 1 I-resin of precursor peptide synthesis：Using resin as carrier, by solid-phase synthesis, addition protection acid, condensing agent and activator to Peptide systhesis reactor, according to Amino acid in the secondary sequence to Thymosin alpha 1 is activated, is condensed, microwave reaction, deprotection reaction and washing, is sequentially connected chest Amino acid in the sequences of gland peptide α 1, that is, obtain following Thymosin alpha 1 I-resin of precursor peptide：Fmoc-Ser(tBu)-Asp(OtBu)-Ala-Ala-Val-Asp(OtBu)-Thr(tBu)-Ser(tBu)-Ser(tBu)- Glu(OtBu)-Ile-Thr(tBu)-Thr(tBu)-Lys(Boc)-Asp(OtBu)-Leu-Lys(Boc)-Glu(OtBu)-Lys (Boc)-Lys(Boc)-Glu(OtBu)-Val-Val-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu(OtBu)-Ala- Glu (OtBu)-Asn (trt)-resin；S2, Thymosin alpha 1 II-resin of precursor peptide synthesis：Acetylation reagent is added into Thymosin alpha 1 I-resin of precursor peptide and carries out the reaction of N-terminal acetylation end socket, obtains following chest II-the resins of precursor peptide of gland peptide α 1：Ac-Ser(tBu)-Asp(OtBu)-Ala-Ala-Val-Asp(OtBu)-Thr(tBu)-Ser(tBu)-Ser(tBu)- Glu(OtBu)-Ile-Thr(tBu)-Thr(tBu)-Lys(Boc)-Asp(OtBu)-Leu-Lys(Boc)-Glu(OtBu)-Lys (Boc)-Lys(Boc)-Glu(OtBu)-Val-Val-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu(OtBu)-Ala- Glu (OtBu)-Asn (trt)-resin；The synthesis of the thick peptide III of S3, Thymosin alpha 1：Cutting reagent is added into Thymosin alpha 1 II-resin of precursor peptide and carries out cleavage reaction, then settles, has obtained Thymosin alpha 1 Thick peptide III；S4, Thymosin alpha 1 synthesis：The thick peptide III of Thymosin alpha 1 is purified and lyophilized purify lyophilized is to obtain following Thymosin alpha 1：Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys- Glu-Lys-Lys-Glu-Val-Val-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH。
- A kind of 2. new method of synthesis in solid state Thymosin alpha 1 according to claim 1, it is characterised in that：Described in step S1 Resin be Wang Resin resins, the substitution value of Wang Resin resins is 0.45mmol/g, described condensing agent and activation Agent is HBTU/DIEA.
- A kind of 3. new method of synthesis in solid state Thymosin alpha 1 according to claim 1, it is characterised in that：Described in step S1 Protection acid be Fmoc- protection acid, the Fmoc- protected amino acids of condensation include Fmoc-Asn (trt)-OH, Fmoc-Glu (Otbu)-OH、Fmoc-Ala-OH、Fmoc-Val-OH、Fmoc-Lys(Boc)-OH、Fmoc-Leu-OH、Fmoc-Asp (Otbu)-OH, Fmoc-Thr (tbu)-OH, Fmoc-Ile-OH and Fmoc-Ser (tbu)-OH, amino acid in the condensation reaction It is 1.5 with resin inventory:1, described setting-up point is 25 DEG C, condensation reaction time 20-30min.
- A kind of 4. new method of synthesis in solid state Thymosin alpha 1 according to claim 1, it is characterised in that：Described in step S1 The microwave reaction time be 20s-25s.
- A kind of 5. new method of synthesis in solid state Thymosin alpha 1 according to claim 1, it is characterised in that：Described in step S1 Deprotection reaction from 20%Pip/DMF be deprotection agent, the addition of deprotection agent is Peptide systhesis reactor volume 1/3~1/2.
- A kind of 6. new method of synthesis in solid state Thymosin alpha 1 according to claim 1, it is characterised in that：Described in step S2 Acetylation reagent be that volume ratio is aceticanhydride：DIEA：DMF=1:1:4 mixed liquor, acetylization reaction time are 20-30min.
- A kind of 7. new method of synthesis in solid state Thymosin alpha 1 according to claim 1, it is characterised in that：Described in step S3 Cutting reagent be that volume ratio is TFA：Water=95:5 mixed liquor, the addition of cutting reagent is Peptide systhesis reactor volume 1/3~1/2, cleavage reaction temperature be 25 DEG C, described being settled into carries out thymic peptide with the absolute ether of -20 DEG C of low temperature precoolings The sedimentation of the thick peptides III of α 1.
- A kind of 8. new method of synthesis in solid state Thymosin alpha 1 according to claim 1, it is characterised in that：Described in step S4 Purifying using reversed-phased high performace liquid chromatographic prepare purifying.
- A kind of 9. new method of synthesis in solid state Thymosin alpha 1 according to claim 8, it is characterised in that：Described anti-phase height Effect liquid phase chromatogram method prepares the condition purified：Chromatographic column prepares post from the C18 that particle diameter is 10um, with A phases：0.1% acetic acid The aqueous solution, B phases：0.1% acetic acid acetonitrile solution is mobile phase, and the separating-purifying of polypeptide is carried out according to following Gradient program：
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711321988.1A CN107857809A (en) | 2017-12-12 | 2017-12-12 | A kind of new method of synthesis in solid state Thymosin alpha 1 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711321988.1A CN107857809A (en) | 2017-12-12 | 2017-12-12 | A kind of new method of synthesis in solid state Thymosin alpha 1 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107857809A true CN107857809A (en) | 2018-03-30 |
Family
ID=61706185
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711321988.1A Pending CN107857809A (en) | 2017-12-12 | 2017-12-12 | A kind of new method of synthesis in solid state Thymosin alpha 1 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107857809A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101104638A (en) * | 2007-06-18 | 2008-01-16 | 苏州中科天马肽工程中心有限公司 | Solid phase synthetic technique for thymosin alpha1 |
| CN101484467A (en) * | 2006-05-10 | 2009-07-15 | Bcn肽类股份有限公司 | Method for synthesizing thymosins |
| CN102199205A (en) * | 2011-03-22 | 2011-09-28 | 海南双成药业股份有限公司 | Synthetic method of polypeptide thymosin alpha1 |
| CN103951744A (en) * | 2014-03-20 | 2014-07-30 | 海南双成药业股份有限公司 | Solid-phase resin and its preparation method and use |
| CN107417786A (en) * | 2017-05-04 | 2017-12-01 | 苏州强耀生物科技有限公司 | A kind of preparation method of Thymosin alpha 1 |
-
2017
- 2017-12-12 CN CN201711321988.1A patent/CN107857809A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101484467A (en) * | 2006-05-10 | 2009-07-15 | Bcn肽类股份有限公司 | Method for synthesizing thymosins |
| CN101104638A (en) * | 2007-06-18 | 2008-01-16 | 苏州中科天马肽工程中心有限公司 | Solid phase synthetic technique for thymosin alpha1 |
| CN102199205A (en) * | 2011-03-22 | 2011-09-28 | 海南双成药业股份有限公司 | Synthetic method of polypeptide thymosin alpha1 |
| CN103951744A (en) * | 2014-03-20 | 2014-07-30 | 海南双成药业股份有限公司 | Solid-phase resin and its preparation method and use |
| CN107417786A (en) * | 2017-05-04 | 2017-12-01 | 苏州强耀生物科技有限公司 | A kind of preparation method of Thymosin alpha 1 |
Non-Patent Citations (3)
| Title |
|---|
| 刘杰等: "FMOC新型固相法合成胸腺素α1 及其反应途径", 《天津药业》 * |
| 吴蕾: "胸腺素α1 的Fmoc 固相合成法", 《化学工业与工程》 * |
| 贡长生主编: "《绿色化学》", 30 June 2008, 华中科技大学出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103497245B (en) | Method for synthesizing thymalfasin | |
| CN104017064B (en) | A kind of method preparing teriparatide | |
| CN109180801B (en) | Method for synthesizing Somalutide | |
| CN106699871A (en) | Preparation method of liraglutide | |
| CN106167514A (en) | The synthesis of a kind of Linaclotide and purification process | |
| CN113880936B (en) | Solid-phase synthesis method of abamectin | |
| CN104177490B (en) | Method for preparing salmon calcitonin acetate by fragment condensation | |
| CN101747426A (en) | Method for synthesizing pramlintide | |
| CN101357938A (en) | Method for synthesizing Exenatide from solid phase polypeptide | |
| CN104788546A (en) | Preparation method of linear peptides containing 24 amino acid residues | |
| CN104098688A (en) | Method for synthesizing thymalfasin | |
| CN106478805A (en) | A kind of preparation method of GLP-1 derivant | |
| CN108059667B (en) | A kind of solid phase synthesis process of Lanreotide | |
| CN112125970B (en) | Synthesis method of semaglutide | |
| CN108070030A (en) | The preparation method of Luo Saina peptides and the like | |
| US11084846B2 (en) | Method for producing peptide | |
| CN111057129B (en) | Preparation method and kit for synthesizing polypeptide containing two pairs of disulfide bonds, and preparation method of pramipexole | |
| CN110903352A (en) | Preparation method of cetrorelix | |
| CN114230653B (en) | Preparation method of chlorotoxin | |
| CN107857809A (en) | A kind of new method of synthesis in solid state Thymosin alpha 1 | |
| CN112321699B (en) | Synthesis method of semaglutide | |
| CN110894227A (en) | Solid-phase synthesis method of liraglutide | |
| CN103992401B (en) | Method for preparing exenatide | |
| CN102875639A (en) | Solid-phase synthetic method of peptide and peptide synthesized by same | |
| CN112125971A (en) | Method for rapidly synthesizing semaglutide by ultrasonic wave |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180330 |