65 results about "Solid-Phase Synthesis Techniques" patented technology

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 relates to a method for synthetizing phosphorodiamidate morpholino oligomer by solid phase. A cheap resin is utilized; Wang resin is as a solid phase carrier; the phosphorodiamidate morpholino oligomer (PMO) structure of which terminal hydroxyl is protected by tert-butyl dimethyl silicon is shown in the description, wherein a structure of basic group B is any one of adenine (A), guanine (G), cytosine (C) and thymine (T). Compared with the existing solid phase synthetic technology, the method provided by the invention can greatly reduce synthetic cost, and can be suitable for mass production of phosphorodiamidate morpholino oligomer.

The invention relates to a solid phase synthesis method of leuprorelin, which uses 4-((1-N-Alkylamino)ethyl) phenoxy-butyramide resin as a solid phase carrier to carry out procedure reaction, and peptide whole protecting resin can be obtained by sequentially carrying out condensation reaction to connect protecting amino-acid; crude peptide can be obtained by cutting the resin by trifluoroacetic acid, and the crude peptide is dissolved in an acetic acid water solution of 5 percent, and the leuprorelin can be obtained by purifying, leaching, condensing and freeze drying the opposite phase high performance liquid chromatograph columns of C18 fillers. The invention uses a novel solid phase resin, and products decorated by peptide chain carbon end alkyl can be obtained directly after finishing assembling the peptide chain by the solid phase synthesis technology and using acid hydrolysis to cut the peptide from the resin after, and the solid phase synthesis method of the leuprorelin is convenient in operation, reduces synthesis steps for synthesizing the leuprorelin greatly and improves the yield.

The invention belongs to the field of biological medicine and specifically discloses a nucleic acid-drug conjugate based on phosphorothioate modified nucleic acid, a drug delivery system and a preparation method thereof. Phosphorothioate groups in the phosphorothioate modified nucleic acid react with groups modified on drug molecules and capable of generating electrophilic reaction with the phosphorothioate groups, so as to form the nucleic acid-drug conjugate; the nucleic acid-drug conjugate can be self-assembled into drug-containing nano-carriers in various forms for drug delivery, in the manner of selecting different nucleotide sequences including functional nucleic acid; compared with the prior art, the invention has the advantages that the nucleic acid-drug conjugate can be acquired through a simple solid-phase synthesis technology, grafting sites and assembling forms of drug molecules on nucleic acid skeleton can be accurately controlled and the method has universality to chemotherapeutic drugs; according to the nucleic acid-drug conjugate, the drug delivery system, the preparation method and the application thereof disclosed by the invention, physicochemical properties and in vivo distribution properties of chemotherapeutic drugs are obviously improved, therapeutic effect thereof can be promoted and combination therapy of gene therapy and chemotherapy can be realized.

The invention relates to manufacture of lubricating oil, in particular to a preparation method of a-piece shaped tungsten disulfide nanometer lubricating oil additive. The preparation method comprises the steps as follows: weighing raw materials which are respectively the tungsten powder and sulfur powder based on the mol ratio of the tungsten to the sulfur of 1: 2.5 to 1: 3; mixing the tungsten powder and the sulfur powder through ball milling, and then adding the mixture to a reaction kettle; transferring the reaction kettle under a protective atmosphere of 600 to 800 DEG C, and annealing for 0.5 to 2 hours at constant temperature; and then naturally cooling to reach the room temperature, so as to obtain the piece-shaped WS2 nanometer lubricating oil additive. According to the preparation method of the piece-shaped tungsten disulfide nanometer lubricating oil additive provided by the invention, a solid phase synthesis technology is applied to synthesizing an inorganic micro-nanometer material; the preparation method has the advantages of being simple in technology, simple and convenient to operate, controllable in temperature, and short in response time; and the preparation method is low in cost, and is suitable for large-scale industrial production; and compared with traditional preparation method, the tungsten powder is adopted to replace the tungsten oxide, thus higher purity of WS2 is achieved, as well as nice appearance; and moreover, higher specific surface area and the tribological properties can be obtained.

The invention relates to a method for synthesizing mono pegylation-thymopentin (mPEG-TP5) by solid phase and liquid phase combination. The method comprises the following steps of: connecting modified polyethylene glycol (mPEG-SCM) to side chain amino of lysine protected by amino by adopting liquid-phase synthesis technology; synthesizing mPEG-TP5 by adopting solid-phase synthesis technology; analyzing and purifying high-efficiency liquid phase through dialysis; and identifying the product structure through nuclear magnetism and mass spectrum. The mono pegylation-thymopentin synthesized by themethod improves the defect that the conventional parent medicament thymopentin has quick biodegradation, poor digesting stability, short biological half-life and the like, and has good application prospect.

The present invention relates to an improved process for the large scale synthesis of cyclic heptapeptide using Fmoc solid phase synthesis technique. The described process assembles the peptide on a solid support resin by coupling to one another by peptide bonds to obtain a peptide wherein the coupling of cysteine to the resin employs a combination of solvents to reduce cysteine racemization. The process described relates to the use of C1-C4 alcohols as total substitute to organic nitriles thus making the process cost effective, non-toxic and eco-friendly.

The invention discloses a preparation method for carbetocin. The preparation method comprises the following steps: subjecting swelled, deprotected and washed amino resin to reacting with an activated protected amino acid solution in a constant-temperature vibrator, carrying out successive introduction into protected amino acids corresponding to first-to-eighth amino acids accounting from the resin and into butyric acid at the tail end of N; subjecting prepared carbetocin precursor peptide 1-amino resin to deprotection, carrying out washing, then carrying out drying until the dried carbetocin precursor peptide 1-amino resin is of a granular shape, adding a cutting reagent, and carrying out a cutting reaction and settling; dissolving a carbetocin precursor peptide II in a solvent, removing impurities by adopting a reversed phase highly-efficient liquid chromatography method, and carrying out liquid-phase cyclizing so as to obtain a crude carbetocin peptide III; and subjecting the crude carbetocin peptide III to purifying and freeze-drying so as to obtain a pure carbetocin polypeptide. The preparation method provided by the invention utilizes an Fmoc solid-phase synthetic principle to develop a solid-phase synthetic technology; and through process optimization, the yield of crude carbetocin is up to 90% or above, so the yield of carbetocin is greatly improved.

The invention relates to the field of medicine, in particular to a polypeptide compound for preventing and treating, or preventing atherosclerosis. Thrombin-inhibited polypeptide 2 is characterized by comprising the sequence of RGDLFRKSADGFIALMKLKK, is prepared by adopting the Fmoc protective solid phase synthesis technology, and can be connected with an adjuvant in a covalence manner, wherein the adjuvant is bovine serum albumin, human serum albumin or polyethylene glycol; the thrombin-inhibited polypeptide 2 can be applied in treating atherosclerosis related diseases; the atherosclerosis related diseases comprise angina pectoris, myocardial infarction, arrhythmia, stroke, encephalanalosis, intractable hypertension, renal insufficiency and other diseases; the atherosclerosis related diseases can be treated in various methods of administration, including subcutaneous or intramuscular injection, intravenous injection or intravenous drip, oral medication, such as pills and capsules, nasal spray and the like. The thrombin-inhibited polypeptide 2 can inhibit the thrombin in a targeted manner, inhibits blood coagulation, and achieves the function of preventing or treating atherosclerosis.

The invention relates to the fields of protein engineering, gene engineering and biomedicines, in particular to a dendritic cell (DC)-based hepatitis B virus T epitope peptide. The technical scheme is that: the DC-based hepatitis B virus T epitope peptide is characterized by consisting of nine amino acid residues in the amino acid sequence of QLFHLCLII. The basic amino acid is taken as a framework, same preset amino acid sequences are simultaneously synthesized on the framework by a solid-phase synthesis technology, a hepatitis B virus is taken as a design target, and the DC-based hepatitis B virus specific epitope peptide is produced by the synthesis technology; the DC is loaded with the epitope peptide in vitro, and the mature DC is injected into bodies of a specific group to specifically generate effects of removing in-vive virus and improving clinical symptoms aiming at hepatitis B virus infection, particularly chronic hepatitis.

The invention discloses a dimer polypeptide with antibacterial and immunomodulating dual functions and application thereof, and belongs to the field of biomedicine. The polypeptide is obtained by thesteps that two stage are divided for preparation by means of a conventional polypeptide solid-phase synthesis technique, then a disulfide bond is formed by thiol pairing of cysteine side chains, and finally semi-preparative reverse high performance liquid chromatography is adopted for purification. Pharmacological experimental results show that the polypeptide has a good inhibition effect on Gram-positive bacteria; the expression of proinflammatory cytokines TNF-alpha, IL-1beta, IL-6 and IL-17 in murine macrophages RAW264.7 induced by lipopolysaccharide can also be inhibited, and the expression of an anti-inflammatory cytokine IL-10 is promoted. Meanwhile, the bifunctional polypeptide shows low hemolytic activity, the artificial preparation is convenient, the pharmacological activity is definite, and the polypeptide has further development value and industrialization potential.

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.