210 results about "Peptide synthesis" patented technology

The invention discloses a cyclic peptide compound as well as a preparation method and application thereof, belongs to the field of polypeptide synthesis and application, and particularly relates to full-protection peptide resin prepared by solid-phase synthesis. Carrying out cutting and monocyclization on the full-protection peptide resin to obtain monocyclic peptide; the monocyclic peptide is subjected to binary cyclization treatment to obtain a cyclic peptide compound Cyclo (His-Lys-Cys-Gly-His-Lys-Cys-Gly-, and a disulfide bond is in bridge connection with Cysamp; and the binary cyclization is cyclized under the action of iodine methanol and ascorbic acid. The cyclopeptide compound prepared by the invention has the advantages of low toxicity, good stability, good antioxidant effect and good anti-inflammatory effect, and the expression of type I collagen can be improved. Therefore, the invention has the advantages of low toxicity, good stability, good antioxidant effect and good anti-inflammatory effect, and can improve the expression of the type I collagen.

Crystalline forms of peptide fragments, methods for their preparation and their use in the preparation of peptides are provided. The crystalline compound of the present invention can be used as an intermediate having improved purity and physical properties for peptide synthesis.

The invention discloses a polypeptide pka15 with a function of inhibiting tumor cell proliferation and application of the polypeptide pka15. The amino acid sequence of the polypeptide pka15 with the function of inhibiting tumor cell proliferation is shown as SEQ ID NO: 1, the nucleotide sequence of the polypeptide pka15 is shown as SEQ ID NO: 2, and the polypeptide pka15 shows good tumor cell proliferation resistance and can be used for preparing drugs or reagents for inhibiting tumor cell proliferation. The polypeptide pka15 disclosed by the invention is simple to synthesize, easy to prepare on a large scale, low in immunogenicity, low in cost, remarkable in effect and convenient for subsequent clinical application and popularization, thereby having a wide application prospect.

The invention relates to a compound of formula (I) wherein X is selected from the group consisting of-O-(CH2) n-wherein n is 0 to 4, R1 and R2 are independently selected from the group consisting of C11-C25 alkyl groups, SP is a spacer, in particular selected from the group consisting of saturated C4-C8 alkyl groups, unsaturated C4-C8 alkyl groups and substituted or unsubstituted C6 aromatic compounds, in particular substituted C6 aromatic compounds are alkyl substituted C6 aromatic compounds, Y is a heteroatom, n is 0 to 4, and R1 and R2 are independently selected from the group consisting of C11-C25 alkyl groups, SP is a spacer, in particular selected from the group consisting of saturated C4-C8 alkyl groups, unsaturated C4-C8 alkyl groups, and substituted or unsubstituted C6 aromatic compounds, in particular substituted C6 aromatic compounds are alkyl substituted C6 aromatic compounds. L is a peptide synthesis linker, in particular selected from the group consisting of-O-and-NH-, L is a peptide synthesis linker, and m is 0 or 1, in particular m is 1.

The invention discloses a preparation method of a myeloid cell triggered receptor 2 protein polyclonal antibody and application of the polyclonal antibody in inhibition of renal fibrosis, and belongs to the technical field of medical molecular biology. The myeloid cell triggered receptor 2 protein is expressed by macrophages, and verification in the mechanism aspect is carried out on the protein; meanwhile, the polyclonal antibody is synthesized according to the polypeptide of the protein, then the effect of the antibody on treating the renal fibrosis is verified again, and a more targeted and personalized method is provided for diagnosis, treatment and management of the renal fibrosis and related kidney diseases.

A Solid Phase Peptide Synthesis (SPPS) device and method of using the same for manufacturing peptides is taught herein. The system comprises at least two reactors, each reactor including a quantity of SPPS resin. The reactors are positioned in series. A de-protecting agent is added to the first reactor and then transferred to the second and third reactors, in series, thereby operating to de-protect the protected N-group. Wash solvent is added to the first reactor and then transferred to the second and this operation repeated several times. Likewise, an amino acid activated ester solution is added, in series, to the first, second and third reactors, thereby operating to couple the amino acid to the de-protected N-group. Wash solvent is added to the first reactor and then transferred to the second and this operation repeated several times prior to the next cycle. The use of the reactors in series reduces the overall solvent required. Online LCMS is also used to monitor progress and identity of reactions happening within the solid phase resin particles.

The invention discloses a synthesis method of tripeptide Fmoc-Pro-Pro-Pro-OH, belongs to the technical field of polypeptide synthesis, and particularly relates to Fmoc-Pro-Pro-Pro-OH prepared by a condensation deprotection reaction of a proline reagent and a proline derivative, the proline reagent comprises Fmoc-Pro-OH or Fmoc-Pro-Pro-OH, and the proline derivative is H-Pro-OtBu. An activating reagent is used in the condensation deprotection reaction, and the mass ratio of the usage amount of the Fmoc-Pro-OH to the usage amount of the activating reagent is 1: (0.1-0.9). Alkali is used in the condensation deprotection reaction, the alkali comprises an alcohol amine compound, the alcohol amine compound is prepared through the reaction of ethanolamine and ethyl 3-bromopyruvate, and the synthesis method of the tripeptide Fmoc-Pro-Pro-Pro-OH is high in yield and purity.

The invention discloses an intelligent polypeptide synthesis process optimization method, equipment and a medium. The method comprises the following steps: 1, loading and preprocessing experimental data of polypeptide synthesis; 2, generating all experimental condition combinations according to experimental data to form a reaction space; 3, converting experimental data into vectorization features; 4, training a Gaussian process regression model based on vectorization features; 5, predicting a potential result corresponding to each group of experimental condition combination in the reaction space according to the Gaussian process regression model; candidate experiment parameters of the next round of experiment are screened out from the potential results according to a Bayesian optimization algorithm; 6, the candidate experiment parameters are applied to an actual experiment, a verification experiment is executed through a microreactor synthesis verification platform, and an experiment result is obtained; and 7, feeding back an experimental result to the Gaussian process regression model, updating model parameters, repeating the steps 5-7 for optimization until an experimental target is met, and outputting an optimal experimental result. According to the invention, efficient optimization of the polypeptide synthesis process can be realized.

The invention relates to the technical field of biological medicine manufacturing, in particular to an environment-friendly and efficient Difelikefalin preparation method. According to the method, a solid-phase peptide synthesis technology is adopted, and the core is that a green mixed solvent system composed of 2-methyltetrahydrofuran and cyclopentyl methyl ether is used for comprehensively replacing traditional toxic solvents such as DMF and DCM. The method comprises the steps of resin swelling, Fmoc deprotection, amino acid coupling, peptide chain cutting, purification and freeze drying, a piperidine / 2-MeTHF solution is adopted in the deprotection, an optimized HATU / DIPEA activation system is adopted in the coupling reaction, a TFA / 2-MeTHF / water mixed solution is adopted in the cutting, and an ethanol-water chromatographic system is adopted in the purification. According to the invention, closed-loop circulation of the solvent is also realized, and 2-MeTHF and CPME are purified through rotary evaporation and reused in the synthesis process. According to the method, high purity and high yield of the product are guaranteed, production toxicity and environmental hazards are remarkably reduced, and the method has excellent industrial application prospects.

The invention relates to the technical field of polypeptide synthesis, and particularly discloses a microwave synthesis method of Angiopep-2. The molecular formula of the Angiopep-2 polypeptide is as shown in formula I in the specification. The method adopts a solid phase polypeptide synthesis strategy and comprises the following steps: (1) coupling Fmoc-Tyr (tBu)-OH to a resin carrier; (2) under the assistance of a microwave synthesizer, sequentially coupling Fmoc protected amino acids from a C end to an N end according to an Angiopep-2 sequence (TFFYGGSRGKRNNFKTEEY, so as to obtain full-protection peptide resin; (3) cracking the resin by using a cracking solution to obtain crude peptide; and (4) purifying through reversed-phase preparative chromatography to obtain the refined peptide. According to the method, the synthesis time is remarkably shortened, the synthesis efficiency is improved, the solvent consumption is reduced, the operation is simple and convenient, the repeatability is high, and the method is suitable for process optimization and large-scale production of Angiopep-2.

The invention discloses a method for synthesizing dipeptide Fmoc-Leu-Aib-OH, and belongs to the field of polypeptide synthesis, the specific preparation method comprises the following steps: under the action of organic alkali and an activating reagent, Fmoc-Leu-OH and H-Aib-OH react to obtain the dipeptide Fmoc-Leu-Aib-OH; the activating reagent comprises at least one of N, N, N ', N'-tetramethyl chloroformamidine hexafluorophosphate, 2-(7-azabenzotriazole)-N, N, N ', N'-tetramethyl urea hexafluorophosphate and benzotriazole-1-yl-oxytripyrrolidinyl phosphorus hexafluorophosphate, and the organic base comprises at least one of N-methylimidazole, N, N-diisopropylethylamine and pyridine. The dipeptide Fmoc-Leu-Aib-OH prepared by the preparation method disclosed by the invention is high in yield, high in purity and high in raw material conversion rate.

The utility model belongs to the field of polypeptide synthesis, and provides a multi-row reaction device for polypeptide synthesis, which comprises a reaction box, a storage component and a swing component, a box cover is hinged on the reaction box, a plurality of rotating shafts are rotatably connected in the reaction box, the storage component is arranged in the middle of the rotating shafts, and a reaction column is arranged in the storage component. A swinging assembly is arranged on the outer side of the reaction box and is used for driving the multiple groups of rotating shafts to rotate to drive the reaction column to swing; the reciprocating driving piece is matched with the T-shaped frame, the T-shaped frame can be driven to drive the row teeth to continuously and transversely reciprocate under the combined action of the motor, the rotating disc and the push column, the row teeth are meshed with the gears to drive the reaction columns to shake left and right, polypeptide synthesis reaction is promoted, reaction efficiency is improved, energy consumption and mechanical abrasion are reduced, and the service life of the reaction columns is prolonged. The push column is adjustably mounted on the turntable through the positioning piece, so that the shaking amplitude of the reaction column can be adjusted as required, and the operability is relatively high.

The invention relates to a chemoenzymatic synthesis method of a high-glucose-type homogeneity mucoprotein core structural domain. The method comprises the following steps: firstly, catalytically synthesizing a key alpha-linked glycosylated amino acid block Fmoc-GalNacalpha-Ser / Thr-OH at a low temperature (-20 DEG C to 0 DEG C); then assembling the building blocks on a repeated polypeptide skeleton rich in proline, serine and threonine at accurate intervals (3-5 amino acid residues) through a solid-phase peptide synthesis technology to form a'sugar chain growth scaffold '; then, a series of high-specificity glycosyl transferases are used for carrying out sequential and directional sugar chain enzymatic extension on the scaffold, and a uniform core structure (such as a core type 3) is constructed; and finally, performing high-efficiency purification by a three-step series method of size exclusion chromatography, ion exchange chromatography and lectin affinity chromatography. The technical bottleneck of inhomogeneity (lt, 70%) of glycoforms in a traditional method is overcome, the mucoprotein core fragment with glycoform homogeneity larger than or equal to 95% and bioactivity highly similar to that of natural mucoprotein can be prepared on a large scale, and the method has wide application prospects in the biomedical fields of mucous membrane protective agents, drug delivery carriers and the like.

This invention relates to the field of peptide synthesis technology, specifically to a type of composition containing long-chain alkane for peptide synthesis and a method for preparing peptides. The composition includes peptide synthesis material A and material B; the general structural formula of peptide synthesis material A is Lca-K-L-AA or L... a -AA; where Lca contains long-chain alkyl and / or long-chain alkenyl groups, L is a polypeptide linker that does not contain long-chain alkyl or long-chain alkenyl groups, and K is an organic fragment or group used to link Lca and L; L a The material B is a polypeptide linker containing long-chain alkyl and / or long-chain alkenyl groups, where AA is an amino acid residue or a peptide containing fewer than 10 amino acid residues; the structure of material B contains long-chain alkyl and / or long-chain alkenyl groups. The compositions of this invention are applied to the synthesis of polypeptides, enabling the use of soluble carbon-based supports for solid-phase polypeptide synthesis.

The invention belongs to the field of polypeptide synthesis and relates to a soluble hydrazino functionalized carrier as well as a preparation method and application thereof. Wherein the structural formula of the soluble hydrazino-functionalized carrier is shown as a formula I. The soluble hydrazino-functionalized carrier is combined with a micro-channel modular reaction device to perform liquid-phase synthesis of Heterophyllin B through a hydrazide method, and compared with a conventional solid-phase synthesis route, the dosage of amino acid is reduced by 60% or above, the dosage of a condensation reagent is reduced by 50% or above, and the yield of the Heterophyllin B is improved. The use amount of the solvent is reduced by 85% or more, and the total yield of the final product Heterophyllin B is also improved by 45%. In conclusion, compared with a conventional solid-phase synthesis method and a large lactamization strategy depending on a coupling reagent, the hydrazide method disclosed by the invention for liquid-phase synthesis of the Heterophyllin B has obvious environmental protection advantages and cost advantages. # imgabs0 #

The present invention relates to a method for preparing peptides via solid-phase peptide synthesis, and in particular, to a method for deprotecting R-AA-(AA) n -PF, which is an Fmoc-protected amino acid building block linked to a resin.

The invention relates to the technical field of polypeptide synthesis, discloses a semaglutide large-fragment coupling process based on an SPPS-LPPS mixing method, and aims to solve the problems that an SPPS fragment is easy to fold and the LPPS coupling efficiency is low when semaglutide is synthesized by an existing SPPS-LPPS mixing method. SPPS is adopted for solid-phase synthesis of a semaglutide 1-21 site fragment I and a semaglutide 22-31 site fragment II, and the fragment quality is guaranteed through optimization of a solid-phase carrier, staged conformation washing and differential activation; according to the method, peptide chain folding and activating agent hydrolysis can be inhibited, the coupling efficiency and the fragment utilization rate can be improved, the purity of a coupling intermediate can be guaranteed, meanwhile, the process stability and economical efficiency can be enhanced, and the industrial production requirements of semaglutide can be met.

The present invention relates to processes for obtaining glucagon-like-peptide-2 (GLP-2) analogues, such as glepaglutide. In particular, the processes described herein use a multi-step purification method of GLP-2 analogues synthesized by solid phase peptide synthesis (SPPS).

The present invention is directed to a method of peptide synthesis, the method comprising reacting a compound of formula (I), or a salt thereof, with a carbodiimide reagent to form an O-acylisourea intermediate; reacting the O-acylisourea intermediate with an additive to form an activated ester; and reacting the activated ester with an amino-containing moiety, which is an amino acid, peptide, or salt thereof, containing an amino group, wherein the amino group forms an amide bond with the carbonyl marked with an * in formula (I), wherein the compound of formula (I) has the structure: TIFF2026501761000047.tif61170 formula (I) where R 1 and R 2 is as defined in the present disclosure. The present invention is also directed to compounds of formula (III) or salts thereof as defined in the present disclosure.

The application discloses a kind of double S-alkyl isothiourea derivatives, its preparation method and application, belong to biochemical technical field.The double S-alkyl isothiourea derivative is the compound shown in general formula 1 or its pharmaceutically acceptable salt, in formula, R is saturated alkane or unsaturated alkane;X is any one of i, ii and iii;I is branched C1-C 20 Saturated alkane or straight-chain C1-C 20 Saturated alkane;II is unsaturated alkane;III is heteroatom-substituted alkane.The application further discloses a preparation method and application of the above-mentioned double S-alkyl isothiourea derivative, a stapled peptide and a preparation method thereof.The double S-alkyl isothiourea derivative of the application can be used for stapled peptide synthesis, and the obtained stapled peptide containing guanidyl structure has the advantages of good water solubility and strong membrane permeability in addition to various advantages of traditional all-carbon hydrogen stapled peptide in polypeptide structure modification.

The invention relates to the technical field of polypeptide preparation, in particular to a solid-phase polypeptide synthesis system and method. The system comprises a flow path switcher, an injection pump, a reagent converging part, a pre-activation reaction module and a coupling reaction module, wherein the flow path switcher comprises a multi-channel switching valve. When the system disclosed by the invention is used for synthesizing the polypeptide, the reaction efficiency is remarkably improved, the use equivalent of amino acid is reduced, the yield and purity of the polypeptide are improved, and long-difficult peptides and modified peptides can be synthesized on a relatively large scale.

This invention provides a class of D-configuration oncolytic peptide-camptothecin conjugates, their preparation methods, and applications, belonging to the fields of peptide preparation and biomedical technology. The steps are as follows: D-configuration peptides are synthesized using a solid-phase peptide synthesis method based on 9-fluorenemethoxycarbonyl. Then, the synthesized D-configuration peptides are covalently linked to a small molecule antitumor drug via a linker group. The D-configuration oncolytic peptide-camptothecin conjugates are obtained through peptide cleavage, separation and purification, and freeze-drying. The D-configuration oncolytic peptide-camptothecin conjugates significantly improve the solubility of camptothecin, exhibiting advantages such as high enzymatic stability, long half-life, and stronger inhibitory effect on tumor cell proliferation. Furthermore, this invention enables spatiotemporal monitoring of the release of camptothecin conjugates, thus possessing good practical application value.

The invention discloses a synthesis method of tilpotide, and belongs to the technical field of pharmacy. According to the method, 2-Cl CTC resin is adopted as initial resin, a solid-phase polypeptide synthesis method is adopted to obtain a polypeptide fragment 1 (1-10 amino acids), then a liquid-phase reaction is performed to prepare salicylaldehyde ester of the full-protection polypeptide fragment 1, and the salicylaldehyde ester of the fragment 1 is obtained after acidolysis; rinkAmide AM resin is used as initial resin, a polypeptide solid-phase synthesis method is used for preparing a polypeptide fragment 2 (the 11th amino acid to the 39th amino acid), then salicylaldehyde ester of a polypeptide fragment 1 and the fragment 2 are subjected to STL chemical connection, then acidolysis is performed to obtain a crude product of the tilpotide, a finished product of the tilpotide is obtained after purification, the purity reaches 99.4% or above, and the yield reaches 47%. According to the method, a two-stage method is adopted, and an STL chemical connection method is used for chemical connection, so that the method has the characteristics of low cost, high yield, high crude peptide purity and the like, and is more suitable for industrial production compared with a current main four-stage process.

Object of the present invention are compounds of formula (1) as protecting groups to perform liquid phase peptide synthesis and a versatile, sustainable and cost-effective industrial process for liquid phase peptide synthesis.

The present invention belongs to the fields of polypeptide synthesis and biomedicine technology, and specifically relates to a polypeptide PM7 and its application in preventing and treating thrombosis. The present invention obtains an original polypeptide from the transcriptome of the salivary gland of the leech Philippine cattle leech, and truncates the original polypeptide to bind to the fibrinogen binding site of thrombin, thereby interfering with the activity of thrombin. Furthermore, {d-Phe}-PRP is added to the N-terminus of the truncated polypeptide, and {d-Phe}-PRP and the truncated polypeptide are connected with a connecting polypeptide to obtain the polypeptide PM7. The polypeptide PM7 of the present invention has the activity of inhibiting thrombin, has a shorter half-life in the body, and is highly safe, thereby achieving the effect of preventing and treating thrombosis.

The present invention provides a polypeptide ligase mutant and a method for preparing a polypeptide. The polypeptide ligase mutant comprises: (a) a protein mutated from the amino acid sequence shown in SEQ ID NO: 1, the mutation comprising a mutation occurring at the S307 site; or (b) a protein having 70% or more identity with the amino acid sequence defined in (a) and having polypeptide ligase activity. The present invention can solve the problem in the prior art of poor activity of polypeptide ligases, and is applicable to the field of polypeptide synthesis.

The present invention relates to a Bsmoc protected lysine salt (1 X ) of formula 1 X , for example the hydrochloride salt (n = 1, HY = hydrochloric acid). The present invention also relates to a method for preparing a Bsmoc protected lysine derivative, which method employs a Bsmoc protected lysine salt of formula 1 X and comprises the step of reacting the epsilon-amino group of lysine with an activated carboxylic acid derivative. Some of the obtained Bsmoc protected lysine derivatives with side chain modifications are used as starting materials in solid phase peptide synthesis.

The present invention relates to methods for performing solid phase peptide synthesis, automated parallel solid phase peptide synthesis, and devices designed to perform such methods. According to the invention, ultrasound at a frequency greater than 25 kHz is applied at least intermittently during the process to the reaction medium in which the solid phase peptide synthesis is carried out.

This invention discloses an interchain disulfide bond Cys A24 -Cys B23 H2Relaxin derivatives with thioether bonds as alternatives and their synthetic methods, wherein the structural formula of the H2Relaxin derivatives is shown below: This invention first utilizes diaminodioic acid molecules to synthesize interchain disulfide bonds (Cys) in a single solid-phase process using an N-fluorenemethyloxycarbonyl (Fmoc) solid-phase polypeptide synthesis method. A24 -Cys B23 The folded refolding precursor of H2Relaxin derivatives with thioether bonds as substitutes was then efficiently obtained via one-step oxidative folding and refolding to yield interchain disulfide bonds (Cys). A24 -Cys B23 The H2Relaxin derivative is replaced by a thioether bond.

The invention provides a polypeptide synthesis platform. The platform comprises a pulse microfluidic system, an ionic liquid assisted supercritical CO2 system, a polypeptide synthesis system and a control system, the pulse microfluidic system provides a reactor, the ionic liquid assisted supercritical CO2 system provides a reaction solvent, the polypeptide synthesis system provides a reactant, and the control system provides reaction conditions. The platform integrates a pulse flow micro-fluidic technology, a pressure-resistant micro-fluidic chip, an ionic liquid-assisted supercritical CO2 system and the like, realizes automatic production, remarkably improves the efficiency, yield and purity of polypeptide synthesis, reduces solvent consumption and waste generation, realizes an efficient and green polypeptide synthesis process, is suitable for various polypeptides, and has wide application prospects. The method is especially suitable for synthesis of long-chain and special peptides which cannot be effectively solved in the prior art.