46 results about "MBHA resin" patented technology

The invention relates to a solid phase synthesis method for ziconotide, which comprises the following steps: an Fmoc-Rink Amide-MBHA resin is taken as a solid phase carrier for program reaction; condensation reactions are orderly performed to link 25 amino acids with protecting groups to obtain a linear peptide complete-protection resin of the 25 amino acids,wherein in three groups of Cyses which form a disulfide bond, the Cyses in the same group are simultaneously linked with one of a Trt, Acm or Mob protecting group, and different groups of the Cyses are linked with different protecting groups; the protecting groups of the three groups of the Cyses are orderly removed; a cyclization reaction is performed to form a disulfide ring bond; a side chain protecting group is removed; and the resin is cut to obtain the ziconotide containing three disulfide rings. The method has the main advantages of few side products, high directive efficiency, simplicity, convenience, high yield of products, and favorability for the purification of the products.

The invention provides a solid-phase preparation method for buserelin. The method comprises the following steps of: 1) preparing a Fmoc-Pro-HMPB-MBHA resin with degree of substitution of between 0.15 and 0.80mmol/g from Fmoc-Pro-OH and a HMPB-MBHA resin with degree of substitution of between 0.2 and 0.9mmol/g by a solid-phase synthesis method; 2) gradually coupling remaining protected amino acid of the Fmoc-Pro-HMPB-MBHA resin according to a peptide sequence to obtain buserelin-HMPB-MBHA resin; 3) cracking the buserelin-HMPB-MBHA resin to obtain fully-protected peptide; and 4) performing ethyl amination, deprotection and purification on the obtained fully-protected peptide to obtain buserelin. The invention aims to provide a buserelin solid-phase synthesis method which has the advantages of high yield, low cost, mild reaction conditions, small environmental pollution and contribution to realizing industrialization.

The invention discloses a preparation method of solid phase peptide synthesis triptorelin, which includes the following steps: with Rink Amide AM resins or Rink Amide MBHA resins as starting materials, amino acids with protective groups are sequentially connected according to solid phase synthesis, so as to obtain protective decapeptide resins, and meanwhile crude products are obtained by sequentially removing Fmoc-protective groups and synchronously removing side-chain protective groups and cutting peptides, and triptorelin elaborate products are prepared after the crude products are separated and purified by C18 (or C8 ) column and freeze-dried. The preparation method is stable in technology, convenient in raw and auxiliary material sources, short in production cycle, high in yield, stable in quality, low in production cost and high in transpeptidase yield. Besides, as the preparation method avoids using poisonous reagents, such as hydrogen fluoride, and the like, the pollution of three wastes is low, purification yield is over 25 percent and each step of transpeptidase yield is above 98 percent; the yield after cutting peptides is 78.8 percent and the total yield is 25.4 percent.

A method for realizing the solid phase synthesis of cetrorelix comprises the following steps that: Fmoc-Linker-MBHA-Resin is used as a starting raw material and is connected in turn with amino acid with Fmoc-protecting groups according to a solid phase synthesis method, so as to obtain protective decapeptide resin; meanwhile, the Fmoc-protecting groups are divested in turn; one sort of HBTU/HOBT or DIC/HOBT is used as condensing agent to carry out synthesized peptide, thereby obtaining protective decapeptide resin; acetylation reaction is carried out, and then protecting group side chain divesting and peptide cutting are carried out synchronously to obtain cetrorelix acetate which is separated and purified through C18 or C8 chromatographic column; finally, cetrorelix acetate acetate or trifluoroacetate is obtained after freeze drying.

The invention relates to a solid-phase synthesis process of a thymosin alpha 1, belonging to the polypeptide solid-phase synthesis technical field. The invention comprises the following steps: a. a Fmoc-Rink Amide AM resin or a Fmoc-Rink Amide MBHA resin is used as carrier, an H2N-Rink Amide AM resin or an H2N-Rink Amide MBHA resin is obtained after deprotection of the Fmoc; b. side chain carboxyl group of Fmoc-Asp-X is connected with resin amino by the method of solid-phase synthesis to obtain the Fmoc-Asp (resin)-X; c. the left amino acid in the sequence is synthesized in solid-phase with the Fmoc strategy; d. after the amino protection group Fmoc of N terminal amino acid is removed, the N terminal amino acid is acetylated by acetic anhydride and pyridine; e. then the acetylated N terminal amino acid is cut by a cracking agent (tri fluoroacetic acid/ benzoylate sulfide/1, 2- dithioglycol/ Anisole) to obtain the thymosin alpha 1; f. crude product of the thymosin alpha 1 is prepared and separated by HPLC to obtain the pure thymosin alpha 1. The invention can increase significantly the yield of the thymosin alpha 1 and decrease the production cost, which is helpful for scale production and has better industrialization prospect.

The invention discloses a method for preparing oxytocin through solid phase polypeptide synthesis, comprising following steps: taking Rink Amide resin (comprising Rink Amide MBHA resin, Rink Amide Am resin) as raw material, taking amino acid protected by Fmoc, TBTU or HBTU/ HOBt as condensing agent, making up amino acid in sequence; adding peptide cutting agent for peptide cutting, adding for precipitation and getting reduced coarse product; adding basic matter, feeding air for oxidation or oxiding with H2O2 with pH being 7.5- 10.0, getting oxidized coarse product; separating and purifying by using C18 or C 8 column and getting final product. The method is characterized by low production cost, simple process, little pollution, high production rate and convenience for industrial production.

The preparation process of solid phase polypeptide synthesized eptifibatide includes the following steps: (1) connecting amino acids one by one with Rink Amide resin, Rink Amide MBHA resin or Rink Amide AM resin as initial material, and Fmoc protected amino aids as monomer, with the last peptide chain being S-benzyl mercapto propionic acid Map(SBzl); (2) adding peptide cutting agent (TFA/HBr/HAc/TIS/EDT) to cut peptide; (3) precipitating and collecting coarse reductant eptifibatide product in ether solvent; (4) dissolving coarse reductant eptifibatide product in water, regulating pH value with ammonia water to 7.5-10.0, introducing air for oxidation, and collecting coarse eptifibatide product; and (5) separating and purifying the coarse product in C18 column to obtain the target product. The present invention has high yield, and is suitable for industrial production.

The invention discloses a preparation method of solid phase peptide synthesis atosiban which includes the following steps: taking Rink Amide resins, Rink Amide MBHA resins or Rink Amide AM resins as starting materials and taking Fmoc amino acids as monomers, amino acids are grafted one by one and mercaptopropionic acids (Map(SX)) are protected by the last peptide chain; after protected nonapeptide resins are obtained, the acellular side-chain protective groups and cutting peptides are synchronized; then cutting peptides is carried out, and reduced crude atosiban is collected; the pH value is adjusted to 7.5 to 10.0, and oxidized crude atosiban is collected; target products are obtained by the separation and purification by preparative HPLC(C18 or C8 column). The preparation method is convenient in material source, simplifies technology and reduces cost; and the preparation method is low in the pollution of three wastes and is high in yield, and the preparation method is convenient for being industrialized and has good industrialization prospect.

The invention discloses a new technology to prepare calf thymus alpha 1 (natural existing in thymus cells of calf and other animals), which uses Fmoc-strategy solid phase method, including the following steps: a. taking any one of Rink Amide PEGA resin, Rink Amide AM resin, Rink Amide MBHA resin or Rink Amide PEGA as the starting material, using the amino acid protected by Fmoc as the monomer to hang resin, connecting amino acids in turn to get a protective 28-peptide resin according to the method of solid-phase synthesis, b. using acetic anhydride to close heads during the process in turn, c. removing Fmoc-protective group in turn, d. synchronizing the removal of side-chain protecting group and the cut of peptide to get a crude, e. purifying the crude with antiphase HPLC to get thymosin alpha 1.

The invention relates to a solid phase synthesis method of goserelin. The method consists of: first reacting RinkAmide MBHA Resin with carbonyldiimidazole (CDI) to obtain an intermediate product, which then reacts with Fmoc-NH-NH2 to obtain Fmoc-NH-NH-CO-NH-Resin, then conducting a programmed reaction, carrying out a condensation reaction in order to connect corresponding amino acids, thus obtaining goserelin resin; performing cutting with a low concentration trifluoroacetic acid solution so as to obtain a crude peptide solution, conducting purification to obtain the goserelin. According to the invention, by reacting a high-activity reactant carbonyldiimidazole with Fmoc-NH-NH2 and Rink Amide MBHA Resin to obtain Fmoc-NH-NH-CO-NH-Resin, the reaction efficiency is greatly improved, so that the reaction can be completed rapidly and efficiently, thus completely solving the problem of difficult synthesis of Fmoc-NH-NH-CO-NH-Resin, and improving the reaction efficiency and yield effectively.

The invention discloses a preparation method for synthesizing proteidin with a solid phase peptide. The technical scheme of the invention comprises the following steps of: connecting amino acids with Fmoc-protection groups in sequence by taking Rink Amide MBHA resin as an initial raw material and taking HBTU/HOBt as a concentration agent according to a solid phase synthesis method to obtain protected heptadeca-peptide resin, wherein Boc-Arg-OH.HCl is taken as a last amino acid; adding a peptide cutting reagent for cutting peptides; adding diethyl ether for precipitating to obtain a reduced crude product; protecting the -SH groups of 5-bit and 14-bit Cys with Trt; oxidizing with hydrogen peroxide at the pH 8.5-10.0; protecting the -SH groups of 7-bit and 12-bit Cys with Acm; oxidizing with iodine in a methanol solution to obtain a dual disulfide bond Cys5-14Cys7-12 crude product; and separating by adopting a C8 high-efficiency liquid phase column for purifying to obtain a target product, wherein the purity of the target product is 99.21 percent, and the total yield is 23.68 percent. The method has the advantages of low production cost, simple process, low environmental pollution, high yield and convenience for industrial implementation.

The invention belongs to the technical field of amino acids, and discloses a synthetic method of carbetocin acetate. The synthetic method comprises the following steps of using Fmoc-Gly-OH and amino resin Rink Amide-MBHA Resin as starting raw materials, firstly, removing Fmoc protecting groups with a 20% DBLK solution, and performing condensation to obtain Fmoc-Gly-Rink Amide-MBHA Resin; sequentially enabling Fmoc protected amino acids to be connected, after connection, removing the Fmoc protecting groups, and performing condensation with 4-bromo butyric acid; removing Mtt protecting groups oncysteine with a weak acid system, and performing cyclization to obtain carbetocin peptide resin; and cutting the peptide resin, and purifying obtained crude peptide, to obtain pure peptide of the carbetocin. The method is simple and feasible, convenient to operate and suitable for large-scale production.

The invention provides a preparation method of plecanatide, and relates to the technical field of polypeptide synthesis. AM resin or MBHA resin is modified through FMPB, H-Leu-OtBu serves as first amino acid to be coupled to the modified resin, amino acid at sites difficult to connect is modified and then is gradually coupled to the modified resin according to the sequence of plecanatide main chain peptide, so that the synthesis difficulty of plecanatide linear peptide is greatly reduced, and the problems of many impurities, low purity, low yield, amino acid racemization and the like in the existing synthesis are solved. The Cys at sites of 4 and 12 in the sequence are subjected to first oxidation bonding and then subjected to column chromatography coarse purification, so that the purity of the obtained plecanatide is improved; the purification liquid is diluted, and the Cys at the 7-site and the 15-site are subjected to the second oxidation bonding, such that the concentration of thepre-oxidized plecanatide line peptide can be reduced so as to reduce the intermolecular disulfide bond during the second oxidation bonding process, and improve the yield of plecanatide; and further, the operation is simple and convenient, and the method is suitable for industrial production.

The invention provides a solid phase synthetic method of ZP120: Ac-Arg-Tyr-Tyr-Arg-Trp-Lys-Lys-Lys-Lys-Lys-Lys-Lys-NH2, which uses Fmoc-Rink Amide-MBHA resin as a material to carry out procedure reaction, and the salt of the ZP120 can be obtained by sequentially connecting amino protecting groups and then removing the groups, acidifying, and removing and cutting side chain protecting groups and resin, and then the ZP120 can be obtained further. The beneficial effect of the invention mainly embodies on: (1) the invention that uses the Fmoc Rink Amide-MBHA resin as a solid phase synthetic carrier is low in cost; (2) N,N-diisopropyl carbodiimide is used as a peptide synthesis condensing agent, and the product process is low in racemization, and the product is good in quality and high in yield; (3) trifluoroacetate is used for cutting the ZP120 peptide resin, and the form of peptide amide can be obtained directly after the cutting, and the subsequent treatment is simple; and (4) the technique is simple and systematic, and is beneficial to industrialization production.

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 1 is KATPIESHQVJAAEKRKC. A preparation method of the inhibitor 1 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 1 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 1 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 agent and the like. The islet amyloid polypeptide inhibitor 1 can targetedly inhibit generation of islet amyloid polypeptide, thereby preventing or treating diabetes.

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 belongs to the field of polypeptide drug preparation methods, and relates to a synthesis method of carbetocin. The synthesis method of carbetocin comprises the following steps of (1) using Rink Amide MBHA Resin as a carrier, performing swelling treatment, and then, sequentially coupling protected Gly, protected Leu, protected Pro, protected Cys, protected Asn, protected Gln, protected Ile and protected Tys to swell Rink Amide-MBHA Resin through a condensation reaction, and performing drying to obtain peptide resin 1; (2) performing reaction on the peptide resin 1 with vinylaceticacid to obtain peptide resin 2; (3) cracking the peptide resin 2 to obtain a carbetocin intermediate I; and (4) performing cyclization reaction on the carbetocin intermediate I to obtain the carbetocin. The synthesis method has the advantages of high reaction selectivity, quick reaction, few by-products and impurities, high yield, safety, environment protection, simplicity and easy operation.