143 results about "Peptide drug" patented technology

Methods and apparatus for protein and drug design using multicapitate (“two or more headed”) neural networks, wherein one head, a sequence head, is trained to generate the sequence of a protein, and another head, a structure head, is trained to generate the structure of the protein; and wherein the neural network is configured to accept a representation of a specified condition as input, and output a representation of a protein's sequence and structure. The structure head and sequence head each have their own loss functions, and the weights of the neural network body are shared, and jointly updated during training. Non-limiting examples of specified input conditions include representations of associated proteins and / or sets of properties of the desired output protein. Some embodiments of the invention include for the design and synthesis of effective peptide drug ligands, synthetic biologic antibody drugs, antibody drug conjugates, and monoclonal antibody (mAb) drugs.

Provided are a sustained-release microsphere for polypeptide drugs, a pharmaceutical formulation thereof, a method for preparing same, and use thereof. The method comprises the following steps: forming an inner aqueous phase; forming an oil phase; forming an outer aqueous phase; and dispersing the inner aqueous phase into the oil phase to give a primary emulsion, then re-dispersing the primary emulsion into the outer aqueous phase to give a pre-secondary emulsion, emulsifying the pre- secondary emulsion to form a secondary emulsion, and finally curing the secondary emulsion to give the sustained-release microsphere. The method features ease to operate, and the obtained sustained-release microsphere possesses ideal drug release behaviors (low early burst release, and stable mid- and later-stage releases) and safety and potency in reducing blood glucose, and is thus suitable for stable, long-term use with good patient compliance.

The invention discloses an anti-aging compound polypeptide solid-in-oil nanosuspension for external use and a preparation method thereof, and belongs to the technical field of medicines. The compound polypeptide solid-in-oil nanosuspension comprises a water-soluble polypeptide drug, a surfactant and an oil phase matrix, the water-soluble polypeptide drug is wrapped by the surfactant, and is uniformly dispersed in the oil-phase matrix after being freeze-dried to form the compound polypeptide solid-in-oil nanosuspension; the water-soluble polypeptide drugs comprise snake venom-like tripeptide, acetyl hexapeptide-8, acetyl tetrapeptide-9, acetyl tetrapeptide-11 and palmitoyl pentapeptide-4, and the average particle size of the drugs in the compound polypeptide solid-in-oil nanosuspension is smaller than 300 nm. The compound polypeptide solid-in-oil nanosuspension has the advantages of being stable in anhydrous phase, good in permeability, high in encapsulation efficiency, good in activity and the like, and is suitable for percutaneous delivery of hydrophilic drugs; the prescription of the solid-in-oil nanosuspension does not contain water, so that the preparation of a stable polypeptide preparation is facilitated, and the solid-in-oil nanosuspension is convenient to store; the composition can be used for anti-aging cosmetics.

The invention belongs to the technical field of big data analysis, and particularly relates to a polypeptide drug pharmacokinetic data analysis platform based on artificial intelligence, which comprises a data collection module, a preprocessing module, a prediction analysis module, a joint verification module and a visual output module. Clinical data collected and processed by the data collection module and the preprocessing module are trained through the prediction analysis module, so that the established model has real data support, and the reliability of the artificial intelligence analysis model is ensured; meanwhile, the joint verification module compares the artificial intelligence analysis model obtained through training with an existing experimental data result and a model structure, and perfects the artificial intelligence analysis model through a model iteration mechanism; the accuracy and authenticity of the analysis result output by the artificial intelligence analysis model are further ensured through multi-dimensional verification, so that reliable technical support is provided for research and development of new drugs.

The invention discloses a scallop skirt ACE inhibitory peptide activity method and system based on deep learning, and relates to the technical field of bioengineering.The scallop skirt ACE inhibitory peptide activity method comprises the steps that a comprehensive data set is obtained based on simulated in-vivo test data and peptide level feature data of different peptides, key features are screened, and a training set and a test set are divided; initializing a random forest model, an SVM model and a logistic regression model, performing independent training by using the training set, and determining an optimal prediction model of the peptide antihypertensive activity based on a prediction result of the test set; extracting importance data of key features based on the optimal prediction model for the antihypertensive activity of the peptide, sorting the importance data, and visually analyzing the antihypertensive activity features, feature importance sorting and model performance of different peptides; and all key results in the analysis process are integrated and systematically stored. According to the method, normal form reference with prediction accuracy and mechanism depth can be provided for clinical transformation of marine bioactive peptides, and AI-driven novel peptide drug research and development are promoted to enter a new stage.

The invention belongs to the technical field of biological medicine, and relates to an oral peptide drug delivery system based on a soybean trypsin inhibitor and core-shell hydrogel, the oral peptide drug delivery system comprises therapeutic polypeptide, KTI and a core-shell structure gel matrix, and the problems that an existing oral peptide delivery system is passively protected and drug burst release is remarkable are solved. A chitosan / sodium tripolyphosphate ionic cross-linked network forms an inner core, a sodium alginate / calcium ion'egg box 'structure cross-linked network forms a shell, and therapeutic polypeptides such as liraglutide and KTI are jointly embedded. Through the pH response characteristic and sequential release design of the core-shell structure, KTI is preferentially and rapidly released in the intestinal environment to inhibit local protease activity, then therapeutic polypeptide is slowly released, and active protection and synergistic interaction are achieved. The invention further provides a specific preparation method and parameters. The polypeptide has the advantages of stable structure in a gastric acid environment, targeted release in intestinal tracts, high encapsulation efficiency, capability of avoiding burst release and the like, and provides a new strategy for efficient delivery of oral polypeptide drugs.

This invention provides an application of the peptide Nod-T3 in the preparation of drugs for treating lung diseases. The Nod-T3 peptide is derived from human protein and has a significant inhibitory effect on chronic lung inflammation and fibrosis caused by smoking. It can be used to treat COPD and other smoking-related lung diseases. It also has high biocompatibility and low toxicity, and has the potential and development value to become a new type of peptide drug.

A peptide sequence mimicking endogenous cofilin-1 incorporates transmembrane amino acid sequences to enhance cellular uptake of the peptide drug. When cofilin peptide drugs are introduced into cancer cells, they affect cancer cell migration and invasion abilities. Furthermore, the peptide sequence can be conjugated with a chelator for cancer diagnosis.

This invention discloses a GLP-1 peptide drug microneedle and its preparation method. The microneedle is composed of PVP, NVP, a photoinitiator, and a GLP-1 receptor agonist. The preparation method includes two steps: material preparation and peptide microneedle patch preparation. First, a certain amount of PVP is dissolved in NVP to prepare a solution with appropriate specific gravity and viscosity. Then, the photoinitiator and GLP-1 receptor agonist are added to the solution to form a liquid system that is as uniformly suspended as possible. Second, the suspension is filled into a microneedle mold, and NVP is polymerized into solid PVP by ultraviolet light irradiation. Under the constraint of the mold, the solid PVP forms the geometric shape of the microneedle. Subsequently, a small amount of NVP is spread evenly on the backing layer of the microneedle and covered with a plastic film. Ultraviolet light irradiation is applied again to crosslink the plastic film with the PVP microneedle, and the microneedle is then peeled out of the mold. The advantage of this application is that it uses PVP to prepare an NVP solution with suitable specific gravity and viscosity, so that the subsequently added drug is uniformly suspended in the solution, thereby improving the uniformity of drug loading on microneedles and increasing the drug loading capacity, which is beneficial to improving the efficacy and consistency of drug efficacy.

The invention discloses a method for detecting polypeptide sequence difference and post-translational modification thereof based on a nanopore system, the nanopore system is constructed in the method, and the nanopore system comprises an alpha-hemolysin nanopore and octa-amino modified gamma-cyclodextrin embedded in the nanopore; the amino acid sequence of the alpha-hemolysin nanopore comprises mutation sites M113R and T145R, and the alpha-hemolysin nanopore is characterized in that the alpha-hemolysin nanopore According to the detection method, polypeptide with negative charges enters a nanopore under the driving of external voltage, an ion current blocking signal is recorded, and the polypeptide sequence difference and post-translational modification are analyzed according to blocking amplitude, duration, noise characteristics and event frequency. The method can detect a peptide chain with the length of 2-10 amino acid residues, can distinguish the post-translational modification state in homopolypeptide composed of 4-10 amino acids and polypeptide by single amino acid resolution, and can be used for protein enzyme digestion product analysis, oligopeptide drug detection and rapid polypeptide identification under the condition of no mass spectrum.

This invention discloses a brush-like peptide drug delivery system, its preparation method, and its applications, belonging to the fields of polymer chemistry and biomedicine. The method includes modifying the amino acid residues of a peptide drug with active functional groups through click or cycloaddition reactions; reacting the modified peptide drug with a polydisulfide backbone through click or cycloaddition reactions to obtain a brush-like peptide drug; and performing charge shielding and bioactivity modification on the lysine residues in the brush-like peptide drug to obtain the brush-like peptide drug delivery system. The brush-like peptide drug delivery system of this invention reduces peptide toxicity, enhances peptide targeting, improves peptide pharmacokinetics, and solves the problem of poor water solubility of some peptide drugs. It can be used in the treatment of tumors, cardiovascular diseases, neurological diseases, pathogenic bacterial or viral infections, or in the development of vaccines.

Problem The purpose of the present invention is to provide a novel method for prevention and / or treatment of opioid tolerance or opioid dependence. Specifically, the purpose of the present invention is to develop peptide-based blockers to block MOR-DOR and KOR-DOR heterodimerization. In addition, the purpose of the present invention is to develop homodimer blockers for MOR, DOR, and KOR which modulate their downstream signaling without affecting their internalization. Solution The present invention is a prophylactic and / or therapeutic agent for the prevention and / or treatment of opioid tolerance or opioid dependence comprising the peptide which inhibits the dimer formation of the opioid receptor, wherein the above opioid receptor dimer is a heterodimer or a homodimer formed from one or two opioid receptors selected from the group consisting of the μ type (MOR), the κ type (KOR), and the δ type (DOR).

This invention discloses a selenylamide-based hydrogenation reaction of acetylacetamide compounds and its application in the modification of selenium-containing peptides and proteins, belonging to the fields of organic chemistry and chemical biology. The reaction involves the reaction of a selenium-containing compound with an acetylacetamide compound in a solvent with the addition of an additive. The applications of this reaction include: 1) selective modification and labeling of selenocysteine ​​in peptides and proteins; 2) cyclization reactions of selenium-containing peptides and selenoproteins; and 3) sequential modification of selenium-containing peptides in the presence of cysteine ​​by precise pH control combined with the hydrogen sulfide reaction of acetylacetamide. This reaction has advantages such as mild conditions, simple operation, fast reaction rate, high yield, good stability, and good selectivity. It provides a new and robust approach for the selective modification and labeling of selenium groups in bioconjugations, peptides, and / or proteins, and also provides a new method for the construction of cyclic peptides, offering a powerful tool for the development of selenium-containing peptide drugs.

The application discloses a polypeptide for targeted recognition of a neuroendocrine tumor marker INSM1 and products and applications thereof, and belongs to the fields of molecular imaging and protein polypeptide drug engineering. Specifically, the application relates to development of a polypeptide with high affinity and specificity to a neuroendocrine tumor marker insulinoma-associated protein 1 (INSM1). The application discloses an amino acid sequence of the polypeptide and related applications. The polypeptide is used for labeling and preparation of a polypeptide probe, can be specifically combined with the INSM1 protein, and can be used for in-vivo and in-vitro imaging of neuroendocrine tumors, so as to overcome a diagnosis difficulty caused by a hidden onset of the neuroendocrine tumor and realize early positioning and qualitative diagnosis.

The present application relates to an oral polypeptide composition system stably absorbed in the gastrointestinal tract, and specifically discloses an oral polypeptide composition. The composition comprises a polypeptide molecule (A), a surfactant (B), an amino acid monomolecular or a bimolecular combination (C). The molecular weight of a peptide drug used as a drug in the oral polypeptide composition is within a range of 0.1 kDa to 20 kDa. The action part of the composition system is small intestine or large intestine; and the polypeptide composition has obviously improved and increased stability and absorbability in the gastrointestinal tract.

Provided, as an anti-SARS-CoV-2 peptide drug, is an optimal salt form of a peptide that binds to a receptor-binding domain (RBD) in SARS-CoV-2.　A sodium or potassium salt of a peptide according to the present invention has, in a direction from an N-terminus to a C-terminus, a first region including a first helix and a second region including a second helix. The first region and the second region each include a site that binds to a receptor-binding domain (RBD) in SARS-CoV-2. A bond is formed between amino acid residues within five residues on the N-terminus side in the sequence of the site that binds to the receptor-binding domain (RBD) in SARS-CoV-2 in the first region and amino acid residues within five residues on the C-terminus side in the sequence of the site that binds to the receptor-binding domain (RBD) in SARS-CoV-2 in the second region, and the peptide binds to the receptor-binding domains (RBD) in SARS-CoV-2.

The invention discloses a method for determining whole-body biological distribution of protein polypeptide drugs, and belongs to the technical field of in-vivo tracking of drugs. Comprising the following steps: mixing a protein polypeptide drug and a fluorescent dye with an NHS group, adding a pH buffer agent without a free amino group, maintaining the pH value of the mixed solution at 7.5-8.5, incubating, and purifying to remove redundant dye so as to obtain a fluorescence labeled product; imaging after in-vivo administration of the fluorescence labeling product, and obtaining the whole-body biological distribution condition of the protein polypeptide drug according to the fluorescence intensity obtained by imaging; or after the fluorescence labeling product is administrated in vivo, blood samples are collected at multiple different time points, fluorescence scanning is carried out, the blood concentration of the protein polypeptide medicine is obtained through calculation, and the whole-body biological distribution condition of the protein polypeptide medicine is obtained. According to the method provided by the invention, the determination process does not need radioactive substances, pollution reagents are not generated or used, and the method is safe and environment-friendly.

Among hospital–acquired infections, Pseudomonas aeruginosa-associated urinary tract infections (UTIs) are mainly caused by indwelling urethral catheters (catheter-associated UTIs or CAUTIs) and are difficult to treat, resulting in high rates of morbidity among hospitalized patients. While antibiotics can successfully treat bacteria in the bladder lumen, they are inefficient at crossing stratified urothelium plasma membranes to kill persistent intracellular bacterial communities (IBCs). Herein, UTI IBCs are targeted by locally delivering the antibiotic gentamicin and / or the steroid hormone estradiol via polymeric nanogels conjugated with a cell-penetrating peptide Cys-Gly-Lys-Arg-Lys (CGKRK - SEQ ID NO:1). This approach delivered more intracellular gentamicin compared to drug delivered in solution in vitro and more estradiol compared to conventional methods. In an acute UTI murine model, the nanogel cell-penetrating peptide drug delivery system facilitated the transport of gentamicin into the urothelium and resulted in > 90% clearance of a uropathogenic P. aeruginosa clinical strain in vivo.

The application relates to the technical field of biological medicine, and particularly provides a pharmaceutical composition containing a peptide drug active molecule and an application thereof. The pharmaceutical composition comprises a peptide drug active molecule and a drug delivery molecule, and the weight ratio of the peptide drug active molecule to the drug delivery molecule is 1:(1-500); the drug delivery molecule is selected from a structure as shown in formula (I) or a pharmaceutically acceptable salt thereof. The application provides an application of the pharmaceutical composition in preparing an oral dosage form drug. The peptide drug active molecule is significantly improved in stability and permeability in a gastrointestinal fluid by being compounded with the drug delivery molecule, so that gastrointestinal absorption of the peptide drug active molecule is increased and oral bioavailability of the peptide drug active molecule is improved.

This invention relates to a non-natural methionine and its synthesis method, using inexpensive and readily available transition metals as catalysts. N Using arylglycine, styrene compounds, and disulfides as raw materials, a series of non-natural methionine compounds were obtained with high selectivity and high yield through a three-component reaction under mild conditions. The compounds prepared in this invention are multifunctional non-natural methionine derivatives, representing a novel class of natural methionine derivatives. They can be used in drug modification, biosensor fabrication, and other fields, possessing significant research and application value and providing new synthetic strategies for the preparation of novel peptide drugs.

The invention discloses an endogenous polypeptide medicine JM2 and application of a target spot of the endogenous polypeptide medicine JM2 in tumor treatment, and relates to the field of biological medicine. The polypeptide drug JM2 is small in molecular weight and easy to absorb, has no obvious toxicity in a cellular level experiment, and has good drug development value and clinical application prospect. The polypeptide medicine JM2 disclosed by the invention has good activity of inhibiting tumor cell proliferation, so that the polypeptide medicine JM2 is used as a tumor inhibitor to help to control growth and diffusion of tumors. The polypeptide medicine JM2 disclosed by the invention has an efficient macrophage phenotype repolarization function, and can generate a remarkable proinflammatory reaction and generate stronger anti-tumor activity, which is possibly crucial for improving the tumor recognition and removal capability of an immune system. The method can be further used for developing infectious diseases and has a wide application prospect.

The present invention relates to the field of target recognition technology, and specifically discloses a method and system for identifying polypeptide drug membrane filtration pollution using a convolutional neural network, wherein the method comprises the following steps: obtaining an image to be identified and a corresponding image sequence; generating a corrected image sequence including the corrected image to be identified; inputting the corrected image to be identified in the corrected image sequence to obtain a high-resolution feature map and a low-resolution feature map; analyzing local area characteristics of the corrected image to be identified to generate a weight parameter group; weightedly fusing the high-resolution feature map and the low-resolution feature map according to the weight parameter group to generate a fused feature map; performing target detection based on the fused feature map to generate a pollution identification result; the method effectively addresses the problems of slight shaking and detail loss under complex imaging conditions, thereby achieving accurate identification of slight pollution targets, having better robustness, being able to effectively identify slight pollution targets, and reducing false alarm and omission rates.

The disclosure provides peptide products comprising a peptide covalently attached to a surfactant moiety which have improved properties, including increased duration of action and bioavailability. The peptide products are useful for treating insulin resistance, diabetes, obesity, metabolic syndrome and cardiovascular diseases, and conditions associated therewith, such as NASH and PCOS.

This invention provides a peptide targeting the degradation of P300, a drug for the prevention and treatment of prostate cancer, a preparation method, and its applications, belonging to the field of protein peptide drug technology. The amino acid sequence of the peptide targeting the degradation of P300 is shown in SEQ ID NO: 1, and its binding constant to P300 protein is 78.3 nM, indicating a strong binding ability to P300 protein. Delivery of the peptide targeting the degradation of P300 to prostate cancer cells can significantly inhibit the proliferation of prostate cancer cells. Simultaneously, the peptide also has the ability to degrade P300. Compared with existing targeted drugs, the peptide drug conjugated with selenium nanoparticles of this invention provides a treatment strategy for drug-resistant and advanced castration-resistant prostate cancer, especially addressing the practical problem of a lack of therapeutic drugs for neuroendocrine prostate cancer.

The invention discloses a double-drug-one-peptide drug delivery system as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The drug loading system provided by the invention comprises Ce (at) MPBMPs, DAP, RosA, MM and E7 homing peptide. The drug loading system can be attached to an intervertebral disc segment corresponding to lumbago in situ, CeO2 is triggered in an inflammatory acid environment by means of a microneedle transdermal drug delivery technology to generate oxygen vortex, and then response release of double-loaded drugs is achieved to synergistically inhibit pathological microenvironment deterioration; meanwhile, endogenous mesenchymal stem cells can be collected specifically through homing peptide E7 modified on the outer layer, the endogenous mesenchymal stem cells are activated in a space-time specific mode to secrete anti-inflammatory external vesicles carrying regulatory factors, and the anti-inflammatory effect is achieved; therefore, the drug loading system can effectively inhibit the deterioration of the key pathological factor inflammation microenvironment of the intervertebral disc degeneration, and realizes the delayed treatment effect on the intervertebral disc degeneration.

The invention belongs to the technical field of polypeptide drugs, and particularly relates to an anti-tumor polypeptide and application thereof. According to the preparation method, Rink amide MBHA amino resin is taken as a solid phase carrier, modification and transformation are carried out according to an amino acid sequence of a template polypeptide H-0 (hymenochirin-1Pa): Ac-LKLSPKTKDTLKKVLKGAIKGAIAIASAMA-NH2, and on the basis that key amino acid residues are reserved, original amino acids are replaced by S5 at the positions of i and i + 4 amino acids, so that the target stapling peptide is obtained. Pharmacological experiments show that the synthesized stapled peptide can significantly inhibit growth and proliferation of tumor cells of liver cancer, lung cancer, glioma and colon cancer, and has an application prospect of being developed into a novel anti-cancer drug.

A peptide sequence mimicking endogenous cofilin-1 incorporates transmembrane amino acid sequences to enhance cellular uptake of the peptide drug. When cofilin peptide drugs are introduced into cancer cells, they affect cancer cell migration and invasion abilities. Furthermore, the peptide sequence can be conjugated with a chelator for cancer diagnosis.

The embodiment of the application discloses an AI+physical hybrid evaluation method based on combination modeling and consistency scoring for short peptide screening. The method firstly constructs a target database based on a large language model, and prepares a short peptide candidate library from natural sources; then a variety of advanced structure prediction models are used to model the short peptide-target protein complex, generating multiple candidate structures; the prediction results are preliminarily screened through an inter-model consistency scoring mechanism; the high-confidence complexes are verified for binding stability through molecular dynamics simulation; finally, multiple indexes such as structure confidence, consistency score and simulation stability are fused, and the weight is optimized through a machine learning model to realize comprehensive evaluation. Experiments show that the method can significantly improve the success rate of screening of potential active short peptides, and the accuracy on an independent test set is improved by about 5% compared with a single model, and has the advantages of multi-model complementation, high prediction reliability and reliable physical verification, and can be widely applied in the fields of modernization of traditional Chinese medicine, development of functional food and research and development of short peptide drugs.

This invention belongs to the field of peptide drugs, specifically relating to an anti-drug-resistant bacterial peptide and its application in pharmaceutical manufacturing. Using Rink amide MBHA amino resin as a solid-phase support, the amino acid sequence of the template peptide raniseptin PL:Ac-GVFDTVKKIGKAVGKFALGVAKNYLNS-NH2 was modified, with amino acid residues 9I and 16F replaced by R8 and S5, respectively, to obtain the target stapling peptide PL-11. Compared to the template peptide PL-0, the stapling peptide PL-11 significantly enhances the antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, and Staphylococcus epidermidis.

The disclosure provides, inter alia, formulations for drug delivery, such as extended release of peptide therapeutics.