62 results about "Polypeptide chain" patented technology

This invention provides a tetrahedral antibody comprising a first, second, third, and fourth domain, wherein the first and second domains are Fab or Fc domains; wherein each of the first and second domains comprise a first polypeptide chain comprising a first N-terminus of the domain, and a second polypeptide chain comprising a second N-terminus of the domain; wherein the first N-terminus of the first domain and the first N-terminus of the second domain are joined to each other by a non-peptidyl linkage, which can be a covalent linkage or a non-covalent linkage between first and second dimerizing polypeptides attached to the first N-termini of the first and second domains, respectively; and wherein the third and fourth domains are attached at their respective C-termini to the second N-termini of the first and second domains, respectively, or the N-termini of the first and second dimerizing polypeptides.

The invention discloses a method for separating an egg white polypeptide chain by adopting a coupling membrane, and particularly relates to the field of egg white polypeptide chains, the method comprises the following steps: S1, mixing fresh egg white with a buffer solution, adjusting the initial acid-base environment and initial temperature of a system, and measuring key basic parameters after dispersion treatment; s3, introducing the pretreated egg white liquid into a first-stage membrane assembly, monitoring separation process parameters, obtaining interception efficiency, dynamically adjusting operation parameters, and enabling permeate liquid to enter a second-stage membrane assembly; s7, monitoring system environment parameters and polypeptide activity, obtaining an activity retention rate, dynamically adjusting supply parameters, and maintaining the polypeptide activity; s8, classifying and collecting products according to molecular weight intervals, evaluating comprehensive separation efficiency, completing separation and verifying product indexes; by constructing an ultrafiltration membrane-nanofiltration membrane-reverse osmosis membrane three-stage coupling separation system and combining a dynamic parameter adjustment mechanism based on interception efficiency, separation selectivity and refined purity, the purity and separation efficiency of a polypeptide product are remarkably improved.

This application relates to facilitating the selective binding between modified VH and VL domains by introducing amino acids with complementary charges into the two domains at novel positions within these domains. These modifications are particularly useful in the design and generation of multispecific antibodies, such as bispecific antibodies, where charge-pair mutations in VH and VL domains can facilitate desired pairing between specific heavy- and light-chain polypeptides. These charge-pair mutations can be used alone or in combination with additional strategies to promote correct pairing of polypeptide chains.

This invention provides an antibody composition with improved stability, exhibiting reduced fragmentation of the antibody polypeptide chain during manufacturing and subsequent storage. [Solution] This disclosure relates to improved compositions and methods for treating T cell-mediated diseases and disorders (e.g., autoimmune disorders, graft-versus-host diseases, and graft rejection). Provided are antibody-containing anti-αβTCR binding polypeptides comprising at least one amino acid substitution or modification that enhances the stability of the binding polypeptide by reducing fragmentation of the light chain variable region. Methods provided herein generally involve administering an effective amount of a stabilized, humanized binding polypeptide specific to the alpha-beta T cell receptor (αβTCR) to a subject in need thereof.

The invention provides a three-specificity immune cell adapter-cytokine fusion protein for malignant tumor immunotherapy as well as a preparation method and application of the three-specificity immune cell adapter-cytokine fusion protein. The fusion protein comprises a first binding domain, a second binding domain and a cytokine structural domain which are covalently linked to form a single polypeptide chain or polypeptide compound. The first binding domain is specifically bound with a tumor associated antigen, and the target spot of the first binding domain comprises but is not limited to KK-LC-1, MSLN, HER2, Claudin18.2, Claudin6 and PSMA; the second binding domain is specifically bound with a CD3 protein complex on the surface of the T cell; the cytokine domain is IL2, IL15, IL12, IL21 or a functional variant thereof. The invention also relates to a nucleic acid molecule for coding the fusion protein, an expression vector and application thereof. The fusion protein can be used for immunotherapy of malignant tumors such as colon cancer, gastric cancer, breast cancer, liver cancer, lung cancer and cervical cancer, and has a good application prospect. The invention effectively solves the problems of insufficient T cell activation and limited killing in solid tumor immunotherapy in the prior art.

The invention discloses a bispecific antibody targeting T cells and Her2 positive cells and a fusion protein connected in series with 4-1BBL. Belongs to the technical field of biology. The fusion protein is of a heterotetramer structure formed by connecting two similar heavy polypeptide chains and two similar light polypeptide chains through disulfide bonds, wherein the similar heavy polypeptide chains comprise a heavy chain variable region of a Her2 targeting antibody, a human IgG1 Fc region and a human 4-1BBL extracellular region; the light polypeptide-like chain comprises a light chain variable region of a Her2 targeting antibody, a human antibody light chain constant region and a single chain variable region fragment of a CD3 targeting antibody. The fusion protein can specifically bind to Her2 positive tumor cells and CD3 molecules on the surfaces of T cells at the same time, and provides a key co-stimulation signal by using 4-1BBL connected in series, so that the killing function of the T cells is efficiently activated and enhanced in the local part of the tumor. The fusion protein provides a novel candidate strategy with stronger curative effect, more lasting effect and better safety for immunotherapy of Her2 positive tumors.

The application belongs to the technical field of biological medicine, and relates to an antibacterial polypeptide, a composition and application thereof. The amino acid sequence of the antibacterial polypeptide is shown in SEQ ID NO. 1: KWKIKWPVKWFKM-NH2. Experiments show that the antibacterial polypeptide has broad-spectrum antibacterial activity on gram-positive bacteria and / or gram-negative bacteria, and simultaneously has low cytotoxicity and low hemolyticity. The antibacterial polypeptide provided in the application is composed of 14 amino acids, the polypeptide chain is short, the molecular weight is small, and the antibacterial polypeptide is easy to be artificially synthesized, is a small-molecule polypeptide with high application value, and can be used for preparing a novel antibacterial agent, and has wide application prospects.

This invention proposes a method for screening bisphenol A-specific peptides using molecular simulation, belonging to the field of food safety technology. The method includes the following steps: 1) Through protein stacking and molecular docking, the molecular structure and interactions of bisphenol A-protein cocrystal compounds in a protein structure database are comprehensively analyzed to obtain the receptor protein and the original parent chain; 2) Based on the original parent chain obtained in step 1), the parent peptide is obtained by truncation of the parent peptide segment by analyzing the main active amino acids in the molecular docking results; 3) By performing virtual amino acid mutations on the parent peptide obtained in step 2), a peptide library specifically binding to bisphenol A is constructed, and molecular dynamics is used for preliminary screening of the peptides; 4) The peptide chains screened in step 3) are used as specific recognition elements, and peptides labeled with fluorescein isothiocyanate are used to form specific recognition probes. The specific recognition probes are mixed with bisphenol A, and the peptide sequences with the strongest specific binding ability to bisphenol A are screened based on the different fluorescence differences. This invention is mainly applied to the screening of specific recognition elements for toxic and harmful small molecules, active ingredients, and functional factors. This method avoids the complex preparation steps of antibodies and the cumbersome screening process of aptamers, achieving high-throughput design of specific recognition elements.

Provided is a bone regeneration material that can provide sufficient therapeutic effects when applied to a bone defect site. The bone regeneration material according to the present invention contains a protein (A). The protein (A) has a polypeptide chain (Y) and / or a polypeptide chain (Y'). The total number of the polypeptide chain (Y) and the polypeptide chain (Y') in the protein (A) is 1-100. The polypeptide chain (Y) includes 2-200 contiguous repeats of an amino acid sequence (X), the amino acid sequence (X) being at least one of: the VPGVG sequence (1), which is the amino acid sequence represented by SEQ ID NO: 1; the GVGVP sequence (4), which is the amino acid sequence represented by SEQ ID NO: 4; and the GAHGPAGPK sequence (3), which is the amino acid sequence represented by SEQ ID NO: 3. The polypeptide chain (Y') is derived from the polypeptide chain (Y) by substituting 5% or less of the amino acid residues with lysine and / or arginine residues, and the total number of the lysine and arginine residues is 1-100.

The invention discloses a PD-L1 cell targeting fusion protein connected in series with a TGFBR2 extracellular domain, IL-2 and a receptor thereof, and an application thereof. Belongs to the technical field of biology. The fusion protein provided by the invention is a heterotetramer formed by connecting two similar heavy polypeptide chains and two similar light polypeptide chains through a disulfide bond. The fusion protein realizes triple functions through a single molecule: tumor specific localization is realized through PD-L1 targeting VHH (Vascular Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus); an immunosuppressive factor TGF-beta in a tumor microenvironment is neutralized through TGFBR2 ECD; effect immune cells expressing a medium affinity IL-2 receptor are selectively activated and amplified by the combination of IL-2 and IL-2R alpha. The PD-L1 inhibitor provided by the invention overcomes the multiple problems of limited curative effect of a single drug, high IL-2 systemic toxicity, tumor microenvironment immunosuppression and the like in the existing PD-(L) 1 inhibitor, and provides technical support for detection, prevention and treatment of PD-L1 positive tumors.

The invention discloses an oligopeptide composition, a recombinant polypeptide chain, a recombinant nucleic acid molecule and application. The oligopeptide composition comprises at least one oligopeptide, the amino acid sequence of the oligopeptide is the amino acid sequence of an active domain of HAPLN1 protein, and the oligopeptide composition is used for improving the expression quantity of fibroblasts on the HAPLN1 protein and collagen I.

The application provides a kind of bispecific antibody and its preparation and application, the bispecific antibody includes two chains: from N end to C end in order: VH1 (or VL1), L1, VH2, CH1, the first polypeptide chain of Fc, and from N end to C end in order: VL1 (or VH1), L2, VL2, CL, second polypeptide chain.It is realized tumor selective accumulation by being located in the N end of double antibody structure of the binding domain targeted to tumor associated antigen (TAA), and its shield is located in the inside immune checkpoint antibody fragment to the binding activity of immune checkpoint to reduce systemic activity.

The invention relates to a triple-effect T cell adapter for targeting T cell lymphoma TRBC1. The invention discloses a TRBC1-targeted triple-effect T cell adapter which is composed of an Fc region, a hinge region, a first Fab arm and a second Fab arm, and a third targeting module is covalently connected to the C end of the Fc region to form a Y-shaped triple-head antibody. The first Fab arm and the second Fab arm are respectively combined with TRBC1 and CD3, and the third Fab arm is combined with CD28 or CD137, so that three functions of tumor recognition, T cell recruitment and co-stimulation amplification are integrated. The two polypeptide chains are heterodimerized through CH3 region button mutation, and correct assembly is ensured. The structure supports module interchange, programmable regulation and control of synergistic signals, significantly enhances TRBC1 positive T cell lymphoma killing, reduces toxicity to normal T cells, has high activity and a wide safety window, and is suitable for preparation of related drugs.

A diagnostic, preventive, or therapeutic agent may be used for a myeloproliferative neoplasm. An antibody or a functional fragment thereof that binds to a cleaved mutant CALR protein, may include an antigen-recognition site in (a) a polypeptide chain having an amino acid sequence set forth in SEQ ID NO: 1 or (b) a polypeptide chain having an amino acid sequence having deletion, substitution, or addition of one to several amino acids in SEQ ID NO: 1; and a diagnostic, preventive, or therapeutic agent for a myeloproliferative neoplasm containing the antibody.

The invention relates to the field of enzyme engineering and molecular biology, and discloses a heterologous virus-derived chimeric multifunctional 5 '-'capping' enzyme, and the mRNA vaccine 5 '-'capping' enzyme is formed by sequentially connecting an RNA triphosphatase functional domain derived from rabbit fibroma virus, a guanylyl transferase functional domain and a methyltransferase functional domain derived from flavivirus NS5 protein. According to the invention, RNA triphosphatase, guanylyl transferase and a methyltransferase structural domain with a dual methylation function are integrated into a single polypeptide chain, so that a catalytic process of completing synthesis of a 5'cap 'structure of the mRNA vaccine by one enzyme and one step is realized, the modification process flow of the mRNA vaccine is remarkably simplified, and the consistency and reproducibility of mRNA vaccine production are improved.

The present disclosure provides a use of a dimer in the preparation of a medicament for treating a tumor in a subject in need thereof, and the dimer formed by two polypeptide chains, with each of the two polypeptide chains comprising an antibody Fc subunit, wherein the dimer comprises two or more immunoglobulin single variable domains (ISVDs), at least one of the ISVDs is specific for PD-L1, and at least one of the ISVDs is specific for CTLA4. The present disclosure also provides a method for treating a tumor in a subject in need thereof, wherein the subject is resistant to the therapy of an immune checkpoint inhibitor.

The present invention relates to DNA constructs comprising a novel TIS sequence. The TIS sequence transcribes into an RNA motif that functions as the protein translation initiation site in an mRNA transcript. The DNA construct may further comprise a nucleic acid sequence encoding signal peptide. Additionally, the DNA constructs may also comprise a nucleic acid sequence encoding a recombinant protein or one or more polypeptide chains thereof. The invention further relates to an expression vector, expression cassette and host cell which comprise said DNA constructs. Furthermore, the present invention relates to a recombinant protein expressed by the host cell as well as a method for expressing the recombinant protein.

Described herein are heteromultimeric proteins comprising at least two different polypeptide chains. The polypeptides may comprise Cε3 domain and / or Cε4 domain derived from an immunoglobulin E, and a Cγ2 and / or a Cγ3 domain derived from an immunoglobulin G. The two polypeptide chains may preferentially heterodimerize to promote formation of the heteromultimer. The two polypeptide chains may bind to two different target molecules, e.g. a cancer antigen and a T cell antigen.

A fusion antibody comprising a first polypeptide chain consisting of VH, CH1, hinge and a first Fc and a second polypeptide chain consisting of VL, CL, hinge and a second Fc, wherein one or more cysteine ​​residues (Cys) on the hinge of the first polypeptide chain and the second polypeptide chain are deleted or mutated to other amino acids, and the cysteine ​​residue at position 214 of the CL of the second polypeptide chain is deleted (C214del).

Compounds, proteins, crosslinked proteins, compositions thereof, and methods of making and uses thereof. A compound, which may be an alpha-amino acid, comprises one or more beta-lactam group(s), one or more triazole groups, substituted analogs thereof, or any combination thereof. A protein comprises one or more amino acid residue(s), each residue comprising a beta-lactam group, a triazole group, or a substituted analog thereof. A protein can be made by a recombinant method using one or more compound(s). A cross-linked protein comprises one or more intramolecular crosslink(s) and / or one or more intermolecular crosslink(s). In various examples, a crosslink is formed, e.g., in solution or in vivo, by a proximity enabled beta-lactam ring opening reaction or an acyl transfer reaction between a beta-lactam group or a triazole group and a nucleophilic side-chain group, where both groups are on a single polypeptide or on different polypeptide chains. Crosslinked protein(s) can be used in methods of treatment.

Techniques regarding antigen-binding proteins that can bind to CoV (e.g., SARS-CoV-2) variants are provided. For example, one or more embodiments described herein can comprise an antigen-binding protein that can comprise a heavy polypeptide chain variable region with an amino acid sequence that is a variant of SEQ ID NO: 7. The amino acid sequence can comprise at least one amino acid substitution selected from the group consisting of: R50D, R50E, R50W, R50F, R50Y, R50L, R50V, R50I, R50Pho, I54D, I54E, I54W, I54F, I54Y, I54Pho, L55D, L55E, L55W, L55F, L55Y, and L55Pho.

The invention discloses a multifunctional chimeric hydroxylase, a preparation method of a dual-modified collagen peptide, a synergistic composition and application thereof, and belongs to the technical field of biology. The structure of the multifunctional chimeric hydroxylase sequentially comprises a prolinyl-4-hydroxylase catalytic structural domain, a lysyl hydroxylase catalytic structural domain and a collagen binding structural domain on a single polypeptide chain. According to the multifunctional chimeric hydroxylase disclosed by the invention, on one hand, the problem of low catalytic efficiency caused by poor affinity of natural hydroxylase to hydrolyzed collagen oligopeptide is solved through an anchoring effect of a collagen binding structural domain; and double hydroxylation modification of the collagen oligopeptide by a one-pot method is realized.

The application discloses a VirusTAC platform for tumor cell membrane protein PD-L1 or CD24 targeted degradation and application thereof, and belongs to the technical field of biological medicine. The platform comprises a heterodimer with R1-R2-R3 structure formed by a first polypeptide chain and a second polypeptide chain, wherein R1 is MeV H or a variant thereof; R2 is a linker composed of R4 and R5, R4 is an IgG Fc region; R5 is a linker that can be cut by a protease; and R3 is a target protein binding domain PD-L1 antibody or CD24 antibody. The platform can specifically recognize tumor high-expression receptors and induce rapid endocytosis of cells by means of tumor-specific expression and efficient endocytosis characteristics of Nectin-4, so as to overcome the defects of the existing TPD technology and realize effective regulation of various target proteins.

Provided herein are methods and host cells for producing a polypeptide containing two chains, such as an antibody, half-antibody, antibody fragment, or one-armed antibody. The methods and host cells allow for two-chain polypeptide production using expression of polynucleotides encoding the polypeptide chains from extra-chromosomal polynucleotide(s), and expression of one or more chaperone protein(s) (e.g., peptidyl-prolyl isomerases and / or protein disulfide oxidoreductases) from the host cell chromosome using non-native combination(s) of promoters and translational units encoding a chaperone protein.

This invention discloses a logic-responsive biomolecule carrier based on a phase separation system, its construction method, and its applications. The carrier is based on the attraction between cationic peptides with different logic responses and negatively charged biomolecules such as DNA or RNA, driving liquid-liquid phase separation and forming droplet-like particle structures. The carrier of this invention can selectively use protein kinase A (PKA) to phosphorylate peptides and use matrix metalloproteinases (MMPs) or glutathione (GSH) to cleave the peptide chain, thereby changing the charge density of the peptide to control the controlled release of biomolecules. It exhibits excellent biocompatibility, resistance to enzymatic degradation, and transfection efficiency, enabling effective delivery of biomolecules.

A Dengue virus Envelope Dimer Epitope (EDE) wherein the EDE: c) spans the polypeptides of a Dengue virus Envelope polypeptide dimer; and / or d) is presented on a dimer of Envelope proteins; and / or c) is formed from consecutive or nonconsecutive residues of the envelope polypeptide dimer, wherein the dimer is a homodimer or heterodimer of native and / or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3 and DENV-4. The EDE may be a stabilized recombinant dengue virus envelope glycoprotein E ectodomain (sE) dimer, wherein the dimer is: covalently stabilized with at least one disulphide inter-chain bond between the two sE monomers, and / or covalently stabilized with at least one sulfhydrylreactive crosslinker between the two sE monomers, and / or covalently stabilized by linking the two sE monomers through modified sugars; and / or, covalently stabilised by being formed as a single polypeptide chain, optionally with a linker region, optionally a Glycine Serine rich linker region, separating the sE sequences, and / or non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid, at the dimer interface or in domain 1 (D1) / domain 3 (D3) linker of each monomer. A compound, for example an antibody or antibody fragment that can neutralize more than one Dengue virus serotype, for example an antibody that can bind to an EDE of the invention.

The present disclosure provides polypeptide molecules comprising one or more polypeptide chains and systems, compositions, and methods of use thereof, wherein the polypeptide molecule comprising one or more polypeptide chains (or engineered polypeptide chain) can be used to effect regulation of a target gene in a cell (e.g., an endogenous target gene in a cell).

This disclosure relates to linker polypeptides. In some embodiments, the linker polypeptide comprises one or more polypeptide chains, the one or more polypeptide chains comprising: an IL-2 polypeptide sequence; a first linker, wherein the first linker is adjacent to the IL-2 polypeptide sequence and comprises a protease-cleavable polypeptide sequence; and an inhibitory polypeptide sequence comprising a VHH domain.

Provided are a gel temporary plugging agent and a preparation method and use thereof. The gel temporary plugging agent has a three-dimensional network structure formed by cross-linking an animal protein, which can be degraded into linear polypeptide chains in an acid solution under a low-temperature condition, thereby achieving a temporary plugging effect; it is reinforced by introducing a reinforcing agent structural unit to ensure plugging performance of the gel temporary plugging agent, thereby enabling the gel temporary plugging agent to achieve plugging in low-temperature reservoirs.

Provided are activatable proprotein homodimers comprising two separate but identical polypeptide chains, each chain comprising a fragment antigen-binding (Fab) region that specifically binds to human PD-1 or human PD-L1 or human B7H3, a hinge / Fc domain, a linker, an IL-2 protein, a protease cleavable linker, and an IL-2Rα protein. Also provided are related pharmaceutical compositions and methods of use thereof.