75 results about "Wang resin" patented technology

The invention discloses a method for synthesizing liraglutide. The method comprises the following steps of: 1, selecting Fmoc-Gly-Wang resin and N terminal Fmoc protected and side chain protected amino acid as raw materials, wherein lysine on a 26th site adopts Fmoc-Lys(Mtt)-OH or Fmoc-Lys(Mmt)-OH, histidine on an N terminal adopts Boc-His(Trt)-OH or Boc-His(Boc)-OH; 2, selectively removing a Mtt or Mmt protecting group on the lysine by adopting 1 percent TFA (Trifluoroacetic Acid); 3, sequentially coupling one g-glutamic acid and palmitic acid on a side chain; and 4, cutting resin by the TFA to obtain a crude product of the liraglutide, and carrying out preparative liquid chromatography purification and lyophilization to obtain a pure product of the liraglutide. The method for synthesizing the liraglutide is simple in steps, saves time and labor, is less in difficult sequences in a coupling process, simple and easy to operate during side chain de-protection, less in byproducts and high in yield, and is suitable for industrialized production.

The invention provides a preparation method for linaclotide. The method includes: utilizing a standard Fmoc technology to connect a side chain protected amino acid with Wang resin, adding a condensing agent HBTU and alkali DIPEA, carrying out condensation reaction in a DMF solvent, employing a DMF solution containing 20% hexahydropiperidine to perform de-Fmoc protection, then conducting cutting from the solid phase resin, adding elemental iodine into a sodium phosphate buffer solution to carry out Cysteine oxidation, thus obtaining linaclotide. The preparation method for linaclotide provided by the invention is the technology for highyield synthesis of linaclotide, simplifies the cyclization process and enhances the cyclization yield, and the final product yield reaches 30%-60%. The preparation method has the advantages of simplicity, mild reaction conditions, high yield, and high product purity, is a feasible preparation method for industrialization of linaclotide, and provides good prospects for industrial production.

The invention relates to a method for preparing linaclotide. The method comprises the following steps of A, synthesizing a pentapeptide fragment I of Fmoc-CysCysGluTyrCys-SBzl by a solid-liquid phase method, B, a nonapeptide fragment resin II of H-CysAsn(Trt)ProAlaCys(Trt)Thr(tBu)GlyCys(Trt)Tyr(tBu)-Wang resin by the solid-liquid phase method, C, adding the pentapeptide fragment I into the nonapeptide fragment resin II, carrying out thioester exchange and S-to-N acyl transfer to obtain a novel tetrakaideca-peptide fragment resin, removing a Fmoc protective group, and carrying out pyrolysis to obtain high-purity linaclotide linear peptide, and D, carrying out oxidation by a GSH/GSSH oxidation system to obtain linaclotide. Through thioester exchange and S-to-N acyl transfer, the method for preparing linaclotide is realized and has the advantages of mild synthesis conditions, high product purity, high yield and large-scale production feasibility.

The invention discloses a bright-ala-ruilin preparing method of solid-phase polypeptide, which comprises the following steps: adopting Wang resin or CTC resin as original material to connect amino with protective group to produce protective nonapeptide resin; removing Fmoc-protective group sequently; proceeding side-chain protective group synchronizingly and cutting peptide; connecting ethylamine through ethylamine-to-HOBT to produce crude product; proceeding separation and purifying through C18 (or C8) pillar to produce fine bright-ala-ruilin. The invention avoids the utility of poisonous agent, which improves the purifying, peptide connecting and obtaining rate.

The invention provides a synthetic method of plecanatide. The method comprises the following sequential steps of: performing a programmed reaction on Wang resin as a solid phase carrier, performing condensation reaction successively to connect 16 protective amino acids to obtain linear peptide fully protected resin with 16 amino acids, wherein in two groups of Cys forming a disulfide bond, Cys in the same group are connected to Mmt or Acm at the same time, and the protecting groups connected by Cys in different groups are different; and successively removing the protecting groups of the two groups of Cys, successively performing directional cyclization reactions to form a dithio cyclic bond, and removing the protecting groups on the side chain and cutting resin to obtain plecanatide containing two dithiorings. The method provided by the invention has the beneficial effects that the method can generate few byproducts, and is high in directional efficiency and simple; the product is favorably purified, and the product yield is high.

The invention provides a method for synthesis of bivalirudin in a solid-phase fragment approach. The method comprises: first employing a solid phase stepwise method to synthesize a 13-peptide fragment I-Wang Resin, and a 7-peptide fragment II with the terminal N protected by Fmoc, coupling the two fragments in the solid-phase fragment approach to synthesize bivalirudin -Wang Resin; and finally conducting deprotection, cracking, purification, and freezing drying so as to obtain pure bivalirudin. Compared with existing solid phase stepwise method or liquid phase fragment method, the method of the invention has the advantages of simple technological operation, high yield and purity, small environmental pollution, and easy large-scale production, etc.

The invention relates to the field of medicine synthesis and discloses a method for synthesizing icatibant. The method comprises the following steps: protection arginine of a protecting group is coupled on the N end and the side chain of arginine; the protection arginine and a resin carrier are subjected to esterification reaction under the action of a coupling reagent and a reactivate reagent to obtain peptide resin 1; the resin carrier is Wang resin or HMP; according to amino acid sequence from C end to N end of icatibant and starting from the peptide resin 1, at presence of a condensation reagent and the reactivate reagent, the protection amino-acid are coupled in sequence in an extending manner to obtain icatibant resin eventually; then the icatibant resin is subjected to acid decomposition to obtain the crude icatibant; the crude icatibant is purified to obtain the pure icatibant. According to the invention, as proper Wang resin or HMP is selected, the whole synthesis process is optimized and the total yield of the icatibant is improved significantly; compared with the prior art, the total yield is increased over 20 %.

The invention discloses a coupling oligoarginine and 2 site substituted endomorphin-1 analogue as well as a synthetic method and application thereof, and relates to an endomorphin-1 analogue as well as a synthetic method and application thereof. The coupling oligoarginine and 2 site substituted endomorphin-1 analogue aims at solving the problems that endomorphin-1 is relatively low in biological stability and peripheral administration analgesic activity and has relatively large side effects on the gastrointestinal tract. The synthetic method comprises the following steps: I, pre-treating Wang resin which is protected by 'Fmoc'; II, removing 'Fmoc' protection groups; III, performing amino acid condensation reaction; IV, extending a peptide chain; V, cutting the peptide chain from the resin; and VI, desalting and purifying crude peptides. According to the endomorphin-1 analogue disclosed by the invention, the opioid affinity and agonist activity can be maintained; and meanwhile, the endomorphin-1 analogue has higher biological stability and peripheral administration analgesic activity than that of maternal endomorphin-1, also has the advantages of reducing the side effects of the gastrointestinal tract, and can be used for preparing polypeptide analgesic medicines.

A process for preparing thymopentapeptide (TP-5) includes the reaction between Wang resin and fluorenylmethyloxycarbonyl (FMOC) protected tyrosine to obtain tyrosine resin, condensation reaction on FMOC protected amino acid to obtain protected TP-5 resin, and cracking by trifluoroacetic acid to obtain coarse TP-5 product. Its advantages are high output rate and easy purification.

The invention relates to a method for preparing icatibant. The method specifically comprises the following steps: A) synthesizing fragment Boc-D-Arg-Arg-OH.2HCl by a liquid phase; B) sequentially coupling amino acids having an N-terminal Fmoc protecting group and a side chain protecting group in accordance with the main chain peptide sequence of icatibant by solid-phase synthesis method, wherein coupling of the last two amino acids is performed by the fragment Boc-D-Arg-Arg-OH.2HCl, and the Wang resin is taken as a starting resin; C) cleaving the peptide from the resin, purifying, desalinating and lyophilizing to obtain icatibant, wherein the content of both of deletion peptide impurities des-D-Arg1-icatibant and des-Arg2-icatibant is less than 0.1%. The invention provides a method for preparing icatibant with the advantages of high purity, low cost and capability of large-scale production; the content of impurities, namely, des-D-Arg1-icatibant and des-Arg2-icatibant can be effectively controlled under the premise of the yield of icatibant is not affected by virtue of the method.

The invention discloses a method for preparing high-purity thymalfasin. The preparation method comprises: firstly preparing a first resin polypeptide fragment, a second resin polypeptide fragment, a third resin polypeptide fragment, a fourth resin polypeptide fragment and a fifth resin polypeptide fragment respectively; cleaving the second resin polypeptide fragment, the third resin polypeptide fragment, the fourth resin polypeptide fragment and the fifth resin polypeptide fragment to obtain crude peptide fragments; purifying the obtained second, third, fourth and fifth crude polypeptide fragments respectively; linking each purified polypeptide fragment to the first resin polypeptide fragment; carrying out an acetylation reaction on resin polypeptide fragments to obtain thymalfasin wang resin; cleaving to obtain the thymalfasin crude product; then purifying the obtained thymalfasin crude product twice; and collecting the mobile phase containing thymalfasin in a collection and purification process, evaporating to dryness under reduced pressure and centrifuging to obtain thymalfasin, and vacuum drying to obtain thymalfasin products. The thymalfasin is prepared by the method disclosed by the invention, the reaction time is effectively shortened, the reaction yield and the quality of the final product are improved; and the purity of thymalfasin prepared is more than 99%.

The invention belongs to the field of antimicrobial peptides, and discloses an antimicrobial peptide based on a cell penetrating peptide Tat (49-57) and a synthetic method of the antimicrobial peptide. The antimicrobial peptide is Tat (YG), Tat (YY), Tat (FG) or Tat (FF), and a sequence of a peptide chain is successively as shown by SEQ ID No. 2 to No. 5. The antimicrobial peptide is synthesized by adopting Wang resin as a carrier, adopting Fmoc as an amino acid side chain protection base, adopting a DMF solution of piperidine as a deprotection reagent and adopting HBTU, HOBT and DIEA as amino acid condensing agents in a solid-phase synthetic method. The four derivative antimicrobial peptides have good inhibition efficiency for escherichia coli, salmonella typhimurium, Bacillus subtilis and staphylococcus aureus, and the inhibition rate for some bacteria can be higher than that of the cell penetrating peptide Tat (49-57); and moreover, the hemolytic activity of the four derivative microbial peptides is small, and the concentration when the bacteriostatic activity is played cannot reach the lowest hemolytic concentration.

The invention belongs to the field of pharmacy, and relates to a chemical preparation method of a cyclic decapeptide compound GG-110824. The cyclic decapeptide compound GG-110824 is formed by connecting ten alpha-L-amino acids end to end in sequence, has a structure shown by a formula (I) and is expressed as cyclo(Gly-Leu-Val-Leu-Leu-Val-Pro-Ile-Gly-Leu). The preparation method of the GG-110824 is a chemical preparation method of a solid phase synthesis straight chain peptide precursor and a liquid phase closed ring by taking Wang resin as a solid carrier, HATU/HOAt (2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate/1-Hydroxy-7-azabenzotriazole) as a condensating agent and N,N-dimethylfomamide as a solvent; the GG-110824 is obtained through chromatographic separation of reaction products, and the structure of a prepared product is conformed through monocrystal X-ray diffraction. The preparation method disclosed by the invention is simple in step and high in yield and has a very high practical value.

The invention discloses a method for preparing liraglutide. The technical defects that heavy metal catalysts are used, synthetic steps are complicated, purification is difficult and the like in the prior art are overcome. The technical scheme of the invention comprises the following steps: 1) with Fmoc-Gly-Wang resin as a carrier, coupling 2nd to 12th amino acids one by one by adopting an Fmoc solid phase synthetic method to obtain polypeptide resin I; 2) removing an mmt protecting group of the 11th Lys side chain through acidolysis, modifying Pal-gamma-Glu on the resin, and removing a Dde protecting group through hydrazinolysis to obtain polypeptide resin II; 3) continuously coupling 13th to 31st amino acids to obtain polypeptide resin III; 4) cutting the polypeptide resin III, splitting polypeptide from the resin and simultaneously removing the protecting group of the side chain to obtain a liraglutide crude product; carrying out high-efficient liquid chromatography separation and purification on the liraglutide crude product, and then lyophilizing the liraglutide curde product to obtain liraglutide. The process method for preparing liraglutide adopted by the invention has the characteristics of simple operation, high purity of crude peptide and high comprehensive yield.

The invention discloses a hexapeptide for inhabiting angiotensin transferase and a preparation method thereof. An amino acid residue sequence of the hexapeptide is as below: threonine-proline-threonine-glutamine-glutamine-serine. The hexapeptide has two preparation methods: (1) a preparation method of yeast source enzymolysis separation: a raw material of dried yeast powder is treated with enzymolysis and separation to obtain a yeast polypeptide component with a molecular weight less than 10 kDa; the yeast polypeptide component is further separated and purified by a molecular exclusion chromatography and an anion-exchange column chromatography to obtain the ACE inhibiting hexapeptide; (2) solid phase synthesis method: a solid carrier of Wang resin, an amino protective group of Fmoc- and a condensing agent of HOBT are treated with a peptide grafting reaction, so as to synthesize the ACE inhibiting hexapeptide by a solid phase method. The invention has mild preparation conditions; and according to in vitro activity test, the hexapeptide obtained has inhibiting effect on ACE.

The invention discloses a preparation method and application of a polypeptide drug conjugate with tumor targeting. The polypeptide drug conjugate with the tumor targeting structurally comprises tumortargeting peptide WA1, a non-splitting connector and a cytotoxicity anti-tumor drug. The preparation method of the polypeptide drug conjugate (PDC-WA1) with the tumor targeting adopts a Fmoc solid-phase synthesis method and comprises the following main synthesis steps of: taking Fmoc-Ala-Wang resin as a raw material, after the tumor targeting peptide is synthesized, connecting the synthesized tumor targeting peptide with Fmoc-Acp-OH and chlorambucil in sequence, and carrying out purification by HPLC to obtain the polypeptide drug conjugate with the tumor targeting and anti-tumor activity. Thepreparation method has the advantages of low production cost, low environment pollution, few reaction by-products and low purification difficulty and is simple in reaction operation.

The invention discloses a solid-liquid phase synthesis method of Bremelanotide. The method comprises the following steps: synthesizing an AC-Nle-Asp-O-2-Phipr dipeptide fragment by virtue of a liquidphase method; coupling a main chain and a side chain of the Lys respectively to prolong a peptide sequence, obtaining Fmoc-His(Boc)-D-Phe-Arg(pbf)-Trp(Boc)-Lys(AC-Nle-Asp-O-2-Phipr)-Wang resin, and after the protecting group is removed, cyclizing the main chain and the side chain. The head and the tail are prevented from being folded into a ring, the problem of large steric hindrance of the foldedring is solved, and the influence of the formed peptide on the non-formed peptide is also reduced to the minimum due to the fact that the ring forming sites are closer. In addition, alkali is not adopted for hydrolysis, and corresponding impurities cannot be generated. The Bremelanotide synthesized by the synthesis method is high in purity, low in cost and suitable for large-scale production.

The invention a chimeric peptide based on endomorphin-1 and neurotensin (8-13) and a synthesis method and application thereof. The chimeric peptide solves the problem that the existing endomorphin-1 has short lasting time of easing pain, low pain-easing activity based on peripheral administration and analgesic tolerance and gastrointestinal side effects. The chimeric peptide has an amino acid sequence of Tyr-Pro-Trp-Phe-Gly-Gly-Arg-Arg-Pro-Tyr-Ile-Leu. The synthesis method comprises 1, Fmoc-protective Wang resin pretreatment, 2, removal of a Fmoc-protective gene, 3, amino acid condensation reaction, 4, peptide chain extension, 5, cutting of the peptide chain from resin, and 6, crude peptide desalting and purification. The chimeric peptide has long duration of easing pain and has the advantages of no pain easing tolerance and low side effects on the gastrointestinal tract. The chimeric peptide is used for preparation of polypeptide pain easing drugs.

The invention discloses a synthesis method of semaglutide. The synthesis method comprises the following steps: (1) taking Fmoc-Gly-Wang resin as a solid-phase carrier and removing an Fmoc protection group; gradually coupling amino acids from a C end to an N end in sequence; coupling to 20 amino acid R-Lys (Fmoc)-OH at the N end of a main chain; (2) removing a side chain Fmoc protection groupof the 20 amino acid at the N end of the main chain and coupling side chain amino acids in sequence; (3) removing a 20 amino acid R protection group at the N end of the main chain and coupling residual amino acids of the main chain in sequence according to a peptide sequence to obtain semaglutide full-protection peptide resin, wherein dipeptide fragments are selected as 18 -19 amino acids at the N end and 1 -2 <nd> amino acids at the N end; and (4) cracking and precipitating the semaglutide full-protection peptide resin through a cracking solution to obtain semaglutide crudepeptide. The method disclosed by the invention is simple and convenient; the prepared semaglutide has high purity and industrial production is facilitated.

The invention provides a method for synthesizing monopegylation fixed piont modification thymopoietin, which belongs to the field of biomedicine. According to the method, firstly, a solid phase is adopted for synthesizing TP5 containing protecting groups, the defect that the fluorenylmethyl chloroformate (FMOC) unit removal operation of the method in the prior art is difficult to carry out is avoided, then, the modified polyethylene glycol is connected onto the lysine side chain amino at the fixed point in a liquid phase, the goal of fixed point modification is reached, simultaneously, the space steric hindrance of the solid phase wang resin is avoided through the liquid phase environment, finally, all protecting groups are removed in one step through palladium carbon catalytic hydrogenation to obtain the pegylation thymopoietin with the long-action effect, the synthesis process is simple and convenient, the cost is low, the yield is high (the total yield is higher than 20 percent), and the industrial production is convenient. The pegylation thymopoietin synthesized by the method can not be easily hydrolyzed by esoteric protease, the renal clearance can be obviously reduced because the molecular weight is heavy, and the internal circulation time is greatly prolonged, so the goals of obviously prolonging the half-life period and improving the bioavailability of organisms are reached.

The invention discloses a method for synthesizing liraglutide and belongs to the technical field of polypeptide synthesis. The method of the invention comprises the steps: with Fmoc-Gly-Wang Resin serving as a solid-phase synthesis starting support, performing activation coupling on 29 amino acids from positions 37 to 9 (sequence C end to N end) of liraglutide by means of a novel condensing agentPyBrop (bromotrispyrrolidinophosphoniumhexafluophosphate), wherein Fmoc-Lys(Pal-Glu-OtBu)-OH is used as a raw material in the position 26; Boc-His(Trt)-Osu and Fmoc-Ala-Osu are used to perform condensing in the positions 7 and 8 to obtain a liraglutide all-protected peptide, and cracking precipitation is then performed to obtain liraglutide. The method has the advantages that amino acid coupling efficiency is improved, racemic peptides and deleted peptide impurities generated in the synthesis process of liraglutide are greatly reduced, racemic impurities (D-His7 and D-Ala8) which are very similar to the product in property are particularly effectively inhibited or reduced, the purity of the crude product is improved, the purification difficulty is reduced, and industrial scaled productionis facilitated.

The invention provides a multi-site modified enkephalin and neurotensin (8-13) coupled cycled hybrid peptide, a compounding method and an application thereof and relates to a cycled hybrid peptide, the compounding method and the application thereof. The invention aims to solve the problems of inferior anti-enzymolysis capacity and non-ideal anti-neuropathic pain effect of present opioids. The hybrid peptide is a hybrid peptide 1, a hybrid peptide 2, a hybrid peptide 3 or a hybrid peptide 4. The preparation method comprises the following steps: 1) pre-treating 'Fmoc' protected Wang resin; 2) removing 'Fmoc' protecting groups; 3) triggering condensation reaction of amino acid; 4) prolonging peptide chain; 5) forming a disulfide bond; 6) cutting peptide chain from the resin; 7) desalting andpurifying crude peptide. According to the invention, the biological stability of hybrid peptide can be enhanced and an anti-neuropathic pain effect can be endowed, through multi-site unnatural amino acid substitution and cyclizing modification. The hybrid peptide provided by the invention can be used for preparing drugs for relieving neuropathic pain.

Insulin amyloid polypeptide inhibitor, preparation method and application thereof. The invention relates to the field of drugs and particularly relates to an inhibitor 1 compound which can treat diabetes. A sequence of the inhibitor 2 is VLSVAALNHLDKATPIESH. A preparation method of the inhibitor 2 is carried out through Fmoc-protected solid-phase synthetic technology, with Rink amide MBHA resin and Fmoc-Gly-Wang resin as supporters, with 6-chloro-1-hydroxylbenzotriazole and N,N-diisopropyl carbodiimide as condensing agents, and with trifluoroacetic acid as a cutting reagent. The invention also provides an application of the inhibitor 2 for preventing or treating diabetes and complications thereof, wherein the complications comprise diabetic nephropathy, diabetic hypertension, diabetic eye diseases and diabetic neurogenic lesion. The inhibitor 2 can be employed for preventing or treating the diabetes and the complications thereof through various dosing methods, such as subcutaneous injection or intramuscular injection, intravenous injection or intravenous drip, and oral medication, such as pills, capsules, nasal spray agents and the like. The islet amyloid polypeptide inhibitor 2 can targetedly inhibit generation of islet amyloid polypeptide, thereby preventing or treating diabetes.

The invention relates to the preparation of polypeptide medicines, in particular to a method for preparing an anti-tumor adjuvant medicine, namely thymopentin. The method for preparing the thymopentin comprises the following steps of: mixing an amino acid resin, namely polyethylene glycol (PEG)-wang resin-Tyr(tbu)-OH and a super absorbent resin; dissolving Fmoc-Val-OH into a dichloromethane (DCM)/dimethylformamide (DMF) solution, and adding the obtained solution into the mixed resin together with a 1-hydroxybenzotriazole (HOBt)/DMF/ diisopropylcarbodiimide (DIC) mixed solution; sequentially washing by using DMF, ethanol and DCM to finish the connection of the Fmoc-Val-OH; and sequentially connecting Fmoc-Asp(OtBu)-OH, Fmoc-Lys(Boc)-OH and Fmoc-Arg-OH by the same method, performing pyrolysis by using a pyrolysis reagent in which the ratio of trifluoroacetic acid (TFA) to ethylenediamine tartrate (EDT) to water is 95:3:2 after connection, filtering the resin, adding a filtrate into absolute ether, sucking supernatant out after settlement, adding purified water of which the volume is the same as that of a precipitate into the precipitate, shaking, standing, demixing, extracting an aqueous layer by using the absolute ether, washing, concentrating, and freeze-drying a concentrated solution to obtain the thymopentin.