49 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 relates to a novel process for the manufacture of 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-pentaazatricyclo [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. The invention further relates to certain synthetic intermediates for use in the novel process according to the invention. The method according to the invention is particularly suitable for the large-scale production of compounds of formula (I) under GMP conditions. # imgabs0 #

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.

Disclosed are macrocyclic peptide compounds or a salt thereof, which are useful as modulators of TNFα, and pharmaceutical compositions comprising such compounds. These compounds may be useful in treating cancers, inflammatory and autoimmune diseases.

The present disclosure provides novel macrocyclic peptides which inhibit the PD-1 / PDL1 and PD-L1 / CD80 protein / protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.

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.

Methods and compositions for generating novel proteins comprise a genetically encoded macrocyclic peptide fused to an immunoglobulin Fc region, referred to as “cyclopeptibodies.” Methods and compositions are provided for making cyclopeptide-Fc region fusion proteins from genetically encoded, ribosomally produced artificial polypeptides. These methods are based on the genetic fusion of an immunoglobulin Fc region to an artificial precursor polypeptide comprising a non-canonical amino acid residue carrying a thiol-reactive functional group; and a cysteine residue that is positioned either upstream or downstream of the non-canonical amino acid in the polypeptide sequence. These methods are based on the ability of the functional group-bearing amino acid and cysteine residue to react after ribosomal synthesis of the polypeptide, so that a cyclic peptide carrying a side-chain-to-side-chain covalent (thioether) linkage is formed and that thioether-linked cyclic peptide is genetically fused to the Fc region of an immunoglobulin.

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 present invention relates to compositions comprising peptide-nucleic acid hybrid molecules of hot spot origin for use in the prevention or treatment of coronavirus infections. It has been proved that the in vitro evolution-based hot spot source peptide-nucleic acid hybrid molecule constructed by the construction method of the invention has high binding affinity to SARS-CoV-2VOC (alpha, beta, gamma, delta and o). In particular, hybrid molecules are demonstrated to exhibit the highest binding resistance in cos with the most mutations. In addition, even when competing with RBD-binding aptamers, macrocyclic peptides, and monoclonal antibodies, hybrid molecules have been observed to have high binding affinity for RBD. In addition, the hybrid molecules prove excellent nuclease resistance and serum stability, indicating that the hybrid molecules not only have anti-SARS-CoV-2, but also have excellent potential as an antiviral neutralizer.

Disclosed herein are mRNA display libraries comprising peptides with non-canonical amino acids and methods of making the mRNA display libraries which may include a plurality of mRNA-linker-macrocyclic peptide molecules comprising AcTyr-[amino acid]m-[PhSec]-[amino acid]n-[Cys]-[linker]-[mRNA]; wherein m and n are each an integer from 0 to 30; and wherein each macrocyclic peptide comprises a thioether linkage and is according to formula I: wherein R comprises [linker]-[mRNA].

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 a preparation method, a product and application of a carbamido-containing macrocyclic peptide compound, and belongs to the technical field of organic synthesis of peptide macrocyclization. The preparation method comprises the following steps: dissolving polypeptide containing two exposed amino groups in an organic solution, and then adding diisocyanate for reaction; then dropwise adding alkali into a reaction system for reaction to obtain a carbamido-containing macrocyclic peptide compound; the polypeptide containing the two exposed amino groups is a polypeptide of N-terminal amino group-side chain amino group or a polypeptide of side chain amino group-side chain amino group. The preparation method provided by the invention has the advantages of high reaction economy, mild conditions, wide substrate applicability, simplicity and convenience in operation and the like. The method can be used for diversity modification of polypeptide / protein, provides a theoretical basis for research on structure functions of polypeptide drugs and compounds with specific functions, and has a wide application prospect in the fields of pharmaceutical chemistry and polypeptide drug innovation.

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.

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.

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.