CN206580758U - Ultrasonic batch reacts the Solid-phase synthesis peptides mechanism for preparing different derived peptides - Google Patents
Ultrasonic batch reacts the Solid-phase synthesis peptides mechanism for preparing different derived peptides Download PDFInfo
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- CN206580758U CN206580758U CN201720228514.1U CN201720228514U CN206580758U CN 206580758 U CN206580758 U CN 206580758U CN 201720228514 U CN201720228514 U CN 201720228514U CN 206580758 U CN206580758 U CN 206580758U
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- supporting plate
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 99
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 55
- 238000010532 solid phase synthesis reaction Methods 0.000 title claims abstract description 32
- 230000007246 mechanism Effects 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 73
- 238000000967 suction filtration Methods 0.000 claims abstract description 30
- 239000012071 phase Substances 0.000 claims abstract description 5
- 238000009830 intercalation Methods 0.000 claims description 3
- 230000002687 intercalation Effects 0.000 claims description 3
- 230000006978 adaptation Effects 0.000 claims 1
- 239000011347 resin Substances 0.000 abstract description 34
- 229920005989 resin Polymers 0.000 abstract description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 14
- 239000007788 liquid Substances 0.000 abstract description 9
- 229910001873 dinitrogen Inorganic materials 0.000 abstract description 6
- 238000003756 stirring Methods 0.000 abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 4
- 230000035484 reaction time Effects 0.000 abstract description 2
- 238000005859 coupling reaction Methods 0.000 description 22
- 230000008878 coupling Effects 0.000 description 14
- 238000010168 coupling process Methods 0.000 description 14
- 238000010511 deprotection reaction Methods 0.000 description 12
- 229920001184 polypeptide Polymers 0.000 description 12
- 150000001413 amino acids Chemical class 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 230000008961 swelling Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical compound ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 1
- 239000003875 Wang resin Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000003746 solid phase reaction Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- Peptides Or Proteins (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
Abstract
The utility model discloses the Solid-phase synthesis peptides mechanism that a kind of reaction of ultrasonic batch prepares different derived peptides, including supporting plate and the reaction cylinder body for containing reaction solution, reaction cylinder base is connected with suction filtration adapter；Suction filtration adapter, which is connected with, vacuumizes flexible pipe；Reaction cylinder deck is connected with some connection grounds, each connection ground is inserted with a Peptide systhesis pipe respectively, and the bottom of Peptide systhesis pipe is provided with core filter core；The middle part of Peptide systhesis pipe is provided with frosted connecting portion；Supporting plate is provided with the brace groove being adapted to reaction cylinder body phase, and reaction cylinder body is placed in brace groove；Supporting plate lower surface is fixedly connected with supersonic generator.The utility model promotes the contact between the liquid in reaction cylinder body and Peptide systhesis inner resin tube using supersonic generator, it can also effectively accelerate solid phase synthesis without nitrogen gas stirring, cost is not only reduced compared with conventional nitrogen gas stirring, and substantially reduce the reaction time, and heavy high-pressure nitrogen bottle need not be carried, labor intensity is reduced.
Description
Technical field
The utility model is related to experimental biotechnology field, more particularly to a kind of Solid-phase synthesis peptides device and synthesis
Method.
Background technology
Solid-phase synthesis peptides are that protected amino acid is connected on solid resin, slough blocking group, then will be next
The residue of protected amino acid and first amino acid reacts and forms peptide bond, then sloughs the blocking group of second amino acid,
Next amino acid is reconnected, so circulation goes down to increase peptide chain.In Solid-phase synthesis peptides, solid resin must be used
Reaction substrate.
, it is necessary to using Suction filtration device in Solid-phase synthesis peptides reaction, Suction filtration device include bottle,suction and with bottle,suction phase
The vavuum pump of connection.
In Solid-phase synthesis peptides, the reaction solution for dissolving in activator is Coupling Solution, and the reaction solution for dissolving in deprotection agent is de-
Protect solution.When carrying out peptide solid phase synthesis, usually using Solid-phase synthesis peptides pipe, added in Solid-phase synthesis peptides pipe
Resin, first by resin swelling, is then alternately added deprotection solution and Coupling Solution carries out synthetic reaction.Add deprotection solution
When, resin with deprotection solution slough the reaction of blocking group；When adding Coupling Solution, resin and the band in Coupling Solution
The amino acid of blocking group carries out coupling reaction.
In Solid-phase synthesis peptides, it is often necessary to based on a female peptide, the different derivative in synthesis various mutations site
Peptide, such as when researching and developing polypeptide drug, it is necessary to based on a kind of female peptide, the different derived peptide in synthesis various mutations site, so
The optimal polypeptide drug of drug effect is found from various derived peptides afterwards.
An amino acid is often connected on resin, is required for being adapted using a kind of amino acid sequence specifically with polypeptide
Coupling Solution, connect different amino acid and need to use different Coupling Solutions.Therefore, in the process of Solid-phase synthesis peptides
In, it is necessary to repeatedly change reaction solution.When preparing a variety of derived peptides based on a kind of female peptide, the major part that various derived peptides need
Coupling Solution is identical, but current Solid-phase synthesis peptides device, identical in the Coupling Solution for preparing each derived peptide needs
When, it is also desirable to coupling reaction is carried out respectively when preparing different derived peptides, lacks that can to carry out Solid-phase synthesis peptides in batches anti-
The device and method answered.
, it is necessary to accelerate the progress of solid phase synthesis using nitrogen gas stirring in existing Solid-phase synthesis peptides method, this
It is accomplished by using high-pressure nitrogen bottle, not only cost is higher, and carrying high-pressure nitrogen bottle is wasted time and energy, and is inconvenient.
Utility model content
The purpose of this utility model, which is that offer is a kind of, to carry out Solid-phase Polypeptide by batch when preparing different derived peptides
The device of synthetic reaction, without progress nitrogen gas stirring.
To achieve the above object, ultrasonic batch reaction of the present utility model prepares the Solid-phase synthesis peptides machine of different derived peptides
Structure includes supporting plate and the reaction cylinder body for containing reaction solution, and reaction cylinder base is connected with suction filtration adapter, suction filtration adapter
Provided with suction filtration valve；
Suction filtration adapter, which is connected with, vacuumizes flexible pipe, and vacuumizing flexible pipe is used to connect external Suction filtration device；
Reaction cylinder deck is connected with some connection grounds, and the top of connection ground is in up big and down small hollow taper type；
A Peptide systhesis pipe, the bottom of the bottom intercalation reaction cylinder body of Peptide systhesis pipe and polypeptide are inserted with each connection ground respectively
The bottom of composite tube is provided with core filter core；The middle part of Peptide systhesis pipe is provided with frosted connecting portion, and frosted connecting portion is in being connected mill
The up big and down small hollow taper type that mouth is adapted；
The bottom of each Peptide systhesis pipe is located at same level；Supporting plate is provided with the branch being adapted to reaction cylinder body phase
Groove is supportted, reaction cylinder body is placed in brace groove；Supporting plate lower surface is fixedly connected with supersonic generator.
Supersonic generator is embedded at supporting plate lower surface；Supporting plate is connected with downwards anti-skid rubber cushion.
The utility model promoted using supersonic generator liquid in reaction cylinder body and Peptide systhesis inner resin tube it
Between contact, so as to can also effectively accelerate solid phase synthesis without nitrogen gas stirring, not only dropped compared with conventional nitrogen gas stirring
Low cost, and the reaction time is substantially reduced, and heavy high-pressure nitrogen bottle need not be carried, reduce labor intensity.
Anti-skid rubber cushion is both to above protecting supersonic generator（Supersonic generator is avoided directly to be contacted with extraneous hard thing）, and under
Anti-skidding effect is played, is placed in the Solid-phase synthesis peptides mechanism that ultrasonic batch of the present utility model reaction is prepared to different derived peptides
It is sufficiently stable when on the devices such as experimental bench.
The utility model devises a kind of multichannel Solid-phase synthesis peptides method and special device, carries out Solid-phase Polypeptide conjunction
It is very convenient into reacting, and batch reaction is carried out by the way that different Peptide systhesis pipes is inserted into same reaction cylinder body simultaneously,
The efficiency compared with the past for substantially increasing Solid-phase synthesis peptides, has saved the time of corresponding research.Using a kind of female peptide as base
Plinth, during the different derived peptide in synthesis various mutations site, compared with conventional synthesizer and synthetic method, with prominent height
Efficiency advantage, can a variety of derived peptides of Fast back-projection algorithm, so as to improve searching effect（Such as drug effect）The effect of optimal polypeptides matter
Rate.
In conventional Solid-phase Polypeptide reaction, resin and reaction solution add same Solid-phase Polypeptide reaction tube, and core filter core is then
Positioned at the middle part of many solid phase reaction pipes.This structure also limit the possibility of batch reaction.
Coupling Solution of the utility model when in use according to required for carrying out next step reaction enters to each Peptide systhesis pipe
Row packet, it would be desirable to Coupling Solution identical Peptide systhesis pipe be classified as same group so as to realize that batch reaction provides basis；
The utility model further sets out the technical scheme of some same reaction cylinder bodies of Peptide systhesis pipe correspondence.
Using supersonic generator, the method for packet is added, and multitube corresponds to the structure of same cylinder body, is utility model
People is put forward after long-term poorly efficient repetition reaction experiment by creative thinking, is to realize batch reaction, improve anti-
Answer the key of efficiency.
Brief description of the drawings
Fig. 1 is that the Solid-phase synthesis peptides mechanism that ultrasonic batch reaction of the present utility model prepares different derived peptides removes polypeptide
Structural representation after composite tube；
Fig. 2 is Fig. 1 top view；
Fig. 3 is that the structure for the Solid-phase synthesis peptides mechanism that ultrasonic batch reaction of the present utility model prepares different derived peptides is shown
It is intended to.
Embodiment
As shown in Figure 1 to Figure 3, ultrasonic batch reaction of the present utility model prepares the Solid-phase synthesis peptides machine of different derived peptides
Structure includes supporting plate 1 and for containing reaction solution（Reaction solution is deprotection solution or Coupling Solution）Reaction cylinder body 2, reaction cylinder
The bottom of body 2 is connected with suction filtration adapter 3, and suction filtration adapter 3 is provided with suction filtration valve 4；
Suction filtration adapter 3, which is connected with, vacuumizes flexible pipe 5, and vacuumizing flexible pipe 5 is used to connect external Suction filtration device（Such as vacuum
Pump）；
The reaction top surface of cylinder body 2 is connected with some connection grounds 6, and the top of connection ground 6 is in up big and down small hollow frustum
Shape；It is inserted with respectively under a Peptide systhesis pipe 7, the bottom intercalation reaction cylinder body 2 of Peptide systhesis pipe 7 in each connection ground 6
Portion and the bottom of Peptide systhesis pipe 7 are provided with core filter core 8；The middle part of Peptide systhesis pipe 7 is provided with frosted connecting portion, frosted connecting portion
In with being connected the up big and down small hollow taper type that ground 6 is adapted；Frosted connecting portion is connected ground 6 and blocked in figure 3,
Therefore label is not provided in figure.Frosted connecting portion coordinates with being connected the formation sealing of ground 6.When being reacted, resin is placed on sand
On core filter core 8, liquid can be by core filter core 8, but the resin of solid-state will not pass through core filter core 8.
The bottom of each Peptide systhesis pipe 7 is located at same level；Supporting plate 1 is provided with to be adapted with reaction cylinder body 2
Brace groove 9, reaction cylinder body 2 be placed in brace groove 9；The lower surface of supporting plate 1 is fixedly embedded at supersonic generator 10.
Supporting plate 1 is connected with anti-skid rubber cushion 11 downwards.
The invention also discloses the Solid-phase synthesis peptides machine that different derived peptides are prepared using the reaction of above-mentioned ultrasonic batch
The ultrasonic wave added multichannel polypeptide synthesis method that structure is realized, is carried out according to the following steps successively：
First step is Connection Step, will vacuumize flexible pipe 5 and is connected with external Suction filtration device；Reaction cylinder body 2 is put
Put in brace groove 9, supersonic generator 10 is connected with external power supply；
Second step is resin packing step, in each Peptide systhesis pipe 7 of multichannel Solid-phase synthesis peptides device respectively
The resin for being connected with identical or different amino acid residue loaded after accurate weighing；
Third step is to carry out resin swelling, is specifically：
1. swelling solvent is added into reaction cylinder body 2；
2. will be equipped with each Peptide systhesis pipe 7 of resin respectively by connect ground 6 insert same reaction cylinder body 2 carry out it is molten
Swollen, Peptide systhesis pipe 7 is supported on connection ground 6；
3. supersonic generator 10 is opened, the ultrasonic wave that supersonic generator 10 is produced is transferred to reaction by supporting plate 1
Cylinder body 2, makes the liquid in reaction cylinder body 2 fully be exchanged by core filter core 8 with the liquid inside Peptide systhesis pipe 7, makes
Liquid in reaction cylinder body 2 is fully contacted with resin；It is swelled 30 ± 10 minutes, after resin is fully swelled, closes ultrasonic wave hair
Raw device 10；
4. suction filtration operation is carried out, suction filtration operation is specifically to open suction filtration valve 4, starts Suction filtration device（Such as vavuum pump）, it is right
React cylinder body 2 and carry out suction filtration, the liquid reacted in cylinder body 2 is extracted out out of reaction cylinder body 2；Suction filtration closes suction filtration valve after terminating
4；
Four steps is to carry out deprotection reaction, is specifically：
1. deprotection solution is added into reaction cylinder body 2；
2. supersonic generator 10 is opened, the deprotection solution in reaction cylinder body 2 is fully contacted with resin；This step is held
It is continuous to carry out 30-40 minutes, supersonic generator 10 is closed, the suction filtration operation is carried out；
5th step is washing resin steps, and this step is by solvent（Such as DMF solvent, methanol solvate or carbon dichloride are molten
Agent；DMF solvent is DMF solvent）Add and resin is washed in reaction cylinder body 2, open ultrasonic wave hair
Raw device 10, makes the liquid in reaction cylinder body 2 fully be contacted with resin；This step is persistently carried out 1 minute, closes supersonic generator
10, carry out the suction filtration operation；
This step repeats six times；
6th step is the step of whether detection deprotection reaction completes, and is specifically：
Whether the deprotection reaction for detecting the resin in each Peptide systhesis pipe 7 by ninhydrin completes, for not
The resin of deprotection reaction is completed, the 4th and the 5th step is repeated；
Resin for having completed deprotection reaction, if solid phase synthesis does not terminate all, carries out next step；If
Solid phase synthesis all terminates, then takes out resin from each Peptide systhesis pipe 7, stops reaction；
7th step is to carry out coupling reaction, is specifically：
1. each Peptide systhesis pipe 7 is made a distinction, the Coupling Solution according to required for carrying out next step reaction is to each polypeptide
Composite tube 7 is grouped, it would be desirable to Coupling Solution identical Peptide systhesis pipe 7 be classified as same group；
2. for the same Peptide systhesis pipe 7 for being assembled with resin, by each Peptide systhesis pipe 7 in the group respectively by even
Connect ground 6 and insert same reaction cylinder body 2, Coupling Solution is added into reaction cylinder body 2；
3. supersonic generator 10 is opened, the liquid in reaction cylinder body 2 is fully contacted with resin；This step is persistently carried out
40-80 minutes；Supersonic generator 10 is closed, the suction filtration operation is carried out；Then it is washing resin steps to carry out the 5th step,
Then the 8th step is carried out；
8th step is the step of whether detection coupling reaction completes, and is specifically：
Whether the coupling reaction for detecting the resin in each Peptide systhesis pipe 7 by ninhydrin completes；For not complete
Into the resin of coupling reaction, repeat the 7th step to re-start coupling reaction；Resin for having completed coupling reaction, then enter
The step of row the 4th to the 6th.Wherein, the swelling solvent is DMF solvent；The resin uses Wang resins
Or Rink resins.
The utility model is although the utility model is described in detail with reference to above-described embodiment, the common skill of this area
Art personnel should be understood：The utility model can still be modified or equivalent substitution, without departing from of the present utility model
Any modification or partial replacement of spirit and scope, it all should cover among right of the present utility model.
Claims (2)
1. ultrasonic batch reacts the Solid-phase synthesis peptides mechanism for preparing different derived peptides, it is characterised in that：Including supporting plate and use
In the reaction cylinder body for containing reaction solution, reaction cylinder base is connected with suction filtration adapter, and suction filtration adapter is provided with suction filtration valve；
Suction filtration adapter, which is connected with, vacuumizes flexible pipe, and vacuumizing flexible pipe is used to connect external Suction filtration device；
Reaction cylinder deck is connected with some connection grounds, and the top of connection ground is in up big and down small hollow taper type；It is each
A Peptide systhesis pipe, the bottom of the bottom intercalation reaction cylinder body of Peptide systhesis pipe and Peptide systhesis are inserted with respectively in connection ground
The bottom of pipe is provided with core filter core；The middle part of Peptide systhesis pipe is provided with frosted connecting portion, and frosted connecting portion is in being connected ground phase
The up big and down small hollow taper type of adaptation；
The bottom of each Peptide systhesis pipe is located at same level；It is recessed that supporting plate is provided with the support being adapted to reaction cylinder body phase
Groove, reaction cylinder body is placed in brace groove；Supporting plate lower surface is fixedly connected with supersonic generator.
2. ultrasonic batch reaction according to claim 1 prepares the Solid-phase synthesis peptides mechanism of different derived peptides, its feature
It is：Supersonic generator is embedded at supporting plate lower surface；Supporting plate is connected with downwards anti-skid rubber cushion.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201720228514.1U CN206580758U (en) | 2017-03-10 | 2017-03-10 | Ultrasonic batch reacts the Solid-phase synthesis peptides mechanism for preparing different derived peptides |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201720228514.1U CN206580758U (en) | 2017-03-10 | 2017-03-10 | Ultrasonic batch reacts the Solid-phase synthesis peptides mechanism for preparing different derived peptides |
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| CN206580758U true CN206580758U (en) | 2017-10-24 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111978367A (en) * | 2020-09-17 | 2020-11-24 | 江苏汉肽生物医药有限公司 | Polypeptide solid-phase synthesis mechanism for preparing different derivative peptides through ultrasonic batch reaction |
| CN113646322A (en) * | 2019-01-15 | 2021-11-12 | 奥利弗·约翰内斯·克鲁泽 | Solid phase peptide synthesis method and device |
-
2017
- 2017-03-10 CN CN201720228514.1U patent/CN206580758U/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113646322A (en) * | 2019-01-15 | 2021-11-12 | 奥利弗·约翰内斯·克鲁泽 | Solid phase peptide synthesis method and device |
| CN111978367A (en) * | 2020-09-17 | 2020-11-24 | 江苏汉肽生物医药有限公司 | Polypeptide solid-phase synthesis mechanism for preparing different derivative peptides through ultrasonic batch reaction |
| CN111978367B (en) * | 2020-09-17 | 2023-11-21 | 江苏汉肽生物医药有限公司 | Polypeptide solid-phase synthesis mechanism for preparing different derivative peptides by ultrasonic batch reaction |
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