36 results about "Macrocyclic peptide" patented technology

The present invention relates to compounds of the formulae (I) or (XX) that are panRAS inhibitors for use in a method of treating cancer.

The present invention provides a cyclic peptide compound optionally linked to a nucleic acid, the cyclic peptide compound having a cyclic moiety wherein: (1) the cyclic moiety is composed of 13 or 14 amino acid residues; (2) among the amino acid residues constituting the cyclic moiety, the number of N-substituted amino acid residues is 7 or more, the number of amino acid residues in a single side chain is 3 or fewer, and the number of native amino acid residues is 4 or fewer; and (3) the ClogP / total amide bond (ClogP / total AB) is 1.0 to 1.8.

In accordance with the present disclosure, macrocyclic compounds have been discovered which inhibit the LAG-3 / MHC Class II protein / protein interaction, and may be useful for the amelioration of various diseases, including cancer and infectious 5 diseases.

Macrocyclic peptides (MPs) are a class of compounds that have been shown to be particularly well suited for engaging difficult protein targets. However, their utility is limited by their generally poor cell permeability and bioavailability. The present disclosure reports an efficient solid-phase synthesis of novel MPs by trapping a reversible intramolecular imine linkage with a 2-carbonyl pyridine to create an imidazopyridinium (IP+)-linked ring. This chemistry is useful for the creation of macrocycles of different sizes and geometries, including head-to-side and side-to-side chain configurations. Many of the IP+-linked MPs exhibit far better passive membrane permeability than expected for "beyond Rule of 5" molecules, in some cases exceeding that of much lower molecular weight, traditional drug molecules. This chemistry has been demonstrated to be suitable for the creation of libraries of IP+-linked MPs and show that these libraries can be mined for protein ligands.

The present invention provides a cyclic peptide compound optionally linked to a nucleic acid, wherein the cyclic peptide compound contains a cyclic portion, (1) the cyclic portion is composed of 13 or 14 amino acid residues, (2) among the amino acid residues composing the cyclic portion, the number of N-substituted amino acid residues is 7 or more, the number of amino acid residues having the same side chain is 3 or less, and the number of natural amino acid residues is 4 or less, and (3) ClogP / total amide bond (ClogP / total AB) is 1.0 to 1.8.

In accordance with the present disclosure, macrocyclic compounds have been discovered which inhibit the LAG-3 / MHC Class II protein / protein interaction and may be useful for the amelioration of various diseases, including cancer and infectious diseases.

The present invention relates to the generation of a library of cysteine-enriched macrocyclic peptide sequences expressed on the surface of yeast cells, methods for their preparation and a population of yeast cells genetically modified to express a plurality of disulfide tethered macrocyclic peptide ligands having different structures and amino acid sequences on the surface of yeast cells.

The present disclosure provides engineered polypeptides (e.g., KRED polypeptides), polynucleotides, expression vectors, and host cells comprising the same, methods of producing polypeptides (e.g., KRED polypeptides), and methods of catalyzing the oxidation of an alcohol group into the corresponding ketone or aldehyde that are useful in the process of generating macrocyclic peptides.

In accordance with the present disclosure, macrocyclic compounds have been discovered which inhibit the LAG-3 / MHC Class II protein / protein interaction, and may be useful for the amelioration of various diseases, including cancer and infectious diseases.

This invention belongs to the field of cyclic peptide synthesis and biomedical technology, specifically relating to a cyclic peptide that targets SctV to inhibit T3SS activity and its applications. Specifically, this invention screens a series of macrocyclic peptides targeting InvA (the SctV protein derived from Salmonella T3SS) from a cyclic peptide library and demonstrates their inhibitory effect on T3SS function. Furthermore, the best-performing cyclic peptide, CP-L1, is mutated and optimized to obtain a mutant peptide with the same broad-spectrum antibacterial effect. The cyclic peptide provided by the above technical solution, as a promising antibacterial drug, can be used for the prevention and treatment of diseases mediated by Gram-negative pathogens, thus possessing significant practical application value.

A macrocyclic polypeptide bearing a pharmacophore is produced by reacting (i) a peptide with two reactive groups X1 and X2; and (ii) a reactive compound comprising reactive groups Y1, Y2 and Z, such that X1 forms a bond by reaction with Y1 and X2 forms a bond by reaction with Y2. Reactive group Z is then reacted with a compound bearing a pharmacophore R in benign aqueous conditions. The macrocycles may be displayed in a library, such as a phage display library, and used to biopan for affinity against a selected target.

In accordance with the present disclosure, macrocyclic compounds have been discovered which inhibit the mouse LAG-3 / MHC Class II protein / protein interaction, and may be useful for the amelioration of various diseases, including cancer and infectious diseases.

In accordance with the present disclosure, macrocyclic compounds have been discovered which inhibit the LAG-3 / MHC Class II protein / protein interaction, and may be useful for the amelioration of various diseases, including cancer and infectious diseases.

The utility model discloses a macrocyclic peptide purification ultrafiltration device based on molecular weight screening, which relates to the technical field of macrocyclic peptide purification ultrafiltration and comprises a base, a cavity is arranged in the base, a vibration motor is fixedly mounted on one side of the inner bottom wall of the cavity, a sliding plate is fixedly mounted on one side of the vibration motor, a sliding rod is fixedly mounted at the top of the sliding plate, and a sliding rod is fixedly mounted at the bottom of the sliding rod. The top of the sliding rod penetrates through the base and extends out of the base, and a sliding plate is fixedly mounted at the top of the sliding rod. According to the macrocyclic peptide purification ultrafiltration device based on molecular weight screening disclosed by the utility model, the vibration motor and the sliding plate are arranged, and the vibration motor works to drive the sliding rod on one side of the sliding plate to vibrate in the use process, so that the vertical pipe on the sliding plate vibrates, and the screen mesh is conveniently shaken in the use process; and therefore, the screening effect is achieved, shaking of the screen cloth is kept, blockage caused by the screen cloth is avoided, the subsequent filtering effect of the device is improved, and meanwhile the use convenience of the device is improved.

Disclosed are compositions and / or methods of use of the compositions for patients with neuronal diseases such as AD, Parkinson's, Huntington's, multiple sclerosis, and ALS. In certain embodiments flavonoids alone, or in a pharmaceutical preparation, are administered through the nasal olfactory route. In certain embodiments the flavonoid is apigenin and the neural disease is Alzheimer's. Targeted dosages may affect mitochondrial function in brain neural cells thus ameliorating a neural disease. In some embodiments a porosome complex is administered for reconstitution into a neural cell. In certain embodiments, one or more macrocyclic or linear peptides are administered.

The invention belongs to the field of biotechnology and pharmaceutical industry, and particularly relates to an RGD macrocyclic peptide multivalent antibody recruitment molecule specifically combined with integrin and application of the RGD macrocyclic peptide multivalent antibody recruitment molecule. The multivalent antibody recruitment molecule has an A-B-C structure, A is an antibody hapten structure, B is a connecting arm, and C is RGD cyclic peptide. The multivalent DNP structure is synthesized by using lysine as a skeleton molecule, and then RGD macrocyclic peptide is inoculated through an azide reaction catalyzed by copper ions, so that the RGD macrocyclic peptide multivalent DNP antibody recruitment molecule capable of being combined with an integrin receptor is obtained. A flow cytometry experiment and a cytotoxicity experiment prove that the RGD macrocyclic peptide coupled multivalent DNP antibody recruitment molecule has a good capability of specifically selectively combining an alpha v beta 3 integrin receptor, and has a good toxic effect on tumor cells with relatively high expression abundance of the alpha v beta 3 integrin receptor; therefore, the molecules have potential value in the aspect of cancer targeted therapy.

The invention provides compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12D mutant of Kirsten rat sarcoma (K-Ras) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

The invention provides compounds of Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit mutants of Kirsten rat sarcoma (K-Ras) protein including the G12D mutant and are expected to have utility as therapeutic agents, for example, for treating cancer. The invention also provides pharmaceutical compositions having compounds of Formula (I) or pharmaceutically acceptable salts thereof. Further, the invention provides methods for using the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

Provided herein are cyclic peptide inhibitors of autophagy that bind to LC3. These cyclic peptides may be used to treat diseases or disorders associated with autophagy, such as, for example, cancer, diabetes, cardiovascular disease, and neurological disorders. These cyclic peptides may also be used to sensitize cancers to front-line chemotherapy, immunotherapy, and / or radiation therapy.

The invention discloses a macrocyclic peptide compound apeptide as well as a preparation method and application of the macrocyclic peptide compound apeptide. The chemical structural formula of the macrocyclic peptide compound apeptide disclosed by the invention is as shown in a formula (I) which is described in the specification. Biological activity data results show that the macrocyclic peptide compound apeptide can repair damage of dopaminergic neurons, has a remarkable effect, and can be further developed as a lead medicine for treating nerve injury diseases such as Parkinson's disease.

Disclosed are compositions and / or methods of use of the compositions for patients with neuronal diseases such as AD, Parkinson's, Huntington's, multiple sclerosis, and ALS. In certain embodiments flavonoids alone, or in a pharmaceutical preparation, are administered through the nasal olfactory route. In certain embodiments the flavonoid is apigenin and the neural disease is Alzheimer's. Targeted dosages may affect mitochondrial function in brain neural cells thus ameliorating a neural disease. In some embodiments a porosome complex is administered for reconstitution into a neural cell. In certain embodiments, one or more macrocyclic or linear peptides are administered.

In accordance with the present disclosure, macrocyclic compounds have been discovered which inhibit the LAG-3 / MHC Class II protein / protein interaction, and may be useful for the amelioration of various diseases, including cancer and infectious 5 diseases.

Methods and compositions are provided for the display of genetically encoded macrocyclic peptides on a biological surface. Also provided are nucleic acid molecules, polypeptides, and methods for generating combinatorial libraries of macrocyclic peptides displayed on a biological surface. These methods can be used to produce and screen vast libraries of conformationally constrained peptides in a high-throughput manner, from which macrocyclic peptides with a desired property can be selected and identified.

The present disclosure relates to a composition for preventing or treating coronavirus infection, including a hotspot-derived peptide-nucleic acid hybrid molecule. It was confirmed that in vitro evolution-based hotspot-derived peptide-nucleic acid hybrid molecule prepared using the method of the present invention has high binding affinity for the RBDs of SARS-COV-2 VOCs (alpha, beta, gamma, delta, and omicron). In particular, it was found that the greatest binding tolerance was exhibited in the most highly mutated omicron. Furthermore, the hybrid molecule showed high RBD binding affinity in competition with RBD-binding nucleic acid aptamers, macrocyclic peptides, and monoclonal antibodies. The hybrid molecule also exhibited excellent nuclease resistance and serum stability, indicating potential as virus neutralizer in addition to SARS-COV-2.

The present invention relates to a class of macrocyclic peptides against Acinetobacter baumannii and use thereof. The present invention specifically relates to a compound of formula (III), a tautomer, a stereoisomer, a pharmaceutically acceptable salt, or a prodrug thereof, a method for preparing same, and use thereof in preparing a medicament for treating or preventing infections and related diseases caused by Acinetobacter baumannii.

The invention relates to a novel process for manufacturing 4-[(11S,14S,17S)-14-(4-Aminobutyl)-11-(3-aminopropyl)-17-(1H-indol-3-ylmethyl)-16-methyl-12,15,18-trioxo-2-thia-4,10,13,16,19-pentazatricyclo[19.4.0.03,8]pentacosa-1(25),3(8),4,6,21,23-hexaen-22- yl]benzoic acid (I), or a pharmaceutically acceptable salt thereof. Formula: (I). The invention further relates to certain synthetic intermediates that are useful for the novel process according to the invention, as well as to processes for making those synthetic intermediates. The process according to the invention is particularly suitable for large-scale manufacturing of the compound of formula (I) under GMP conditions.

The present disclosure relates to an efficient and scalable enzymatic process for synthesizing macrocyclic peptides of Formula 1': or salt, hydrate, and / or solvate thereof. The process utilizes engineered ATP-dependent ligase and carboxylesterase enzymes to provide a compound of Formula 1' in large scale while maintaining desired regiochemistry, reduced by-product formation and high yields.

The present invention provides compounds of formula (I): (I) wherein X, Y, R1, R2, and R3 are as described herein, as well as pharmaceutically acceptable salts thereof. Further, the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments for the treatment of diseases and infections caused by bacteria.

In accordance with the present disclosure, macrocyclic compounds have been discovered which inhibit the LAG-3 / MHC Class II protein / protein interaction, and may be useful for the amelioration of various diseases, including cancer and infectious diseases.

The present invention relates to a synthetic peptide and its application thereof. Particularly the present invention discloses a non-cell penetrating, metacyclic synthetic peptide to detect the phosphatidylserine (PS). The present invention discloses the design of metacyclic peptides that mimic the topography of the PS specific membrane binding region of Annexin V. The synthetic peptides of the present invention are suitable for detection of the apoptotic cells, cancer cells, extra cellular vesicles, and function thereof. The present synthetic peptides can be used in atherothrombosis, in vitro diagnostics and immunomodulation.