169 results about "Lysine residue" patented technology

Provided herein are common light chain bispecific antibodies that bind CD38 and CD19. The common light chain bispecific antibodies comprise an anti-CD38 heavy chain variable region and anti CD19 heavy chain variable region that each have a negatively-charged amino acid at a terminal heavy chain variable region position. The common light chain bispecific antibodies comprise further comprise an anti-CD38 heavy chain constant region and anti-CD19 heavy chain constant region that each lack a C-terminal lysine residue. Further provided are nucleic acids encoding such common light chain bispecific antibodies and host cells comprising the nucleic acids. Also provided are methods of making such common light chain bispecific antibodies.

The invention belongs to the technical field of biological medicines, and particularly discloses an epidermal growth factor-linker polypeptide-collagen, and the linker polypeptide has an amino acid sequence as shown in SEQ ID No.1. The linker polypeptide capable of connecting the EGF and the collagen is designed and synthesized, the N end of the linker polypeptide simulates an EGF receptor structure and can be combined with the EGF, and the linker polypeptide is connected with the EGF through non-covalent Van der Waals force, so that the structure of the EGF cannot be damaged; the C terminal of the linker polypeptide is rich in lysine residues, and can be covalently crosslinked to collagen through glutamine transaminase to form EGF-linker polypeptide-collagen. The protein solution taking EGF-linker polypeptide-collagen as active ingredients is low in cytotoxicity and high in biological safety, and meanwhile, the action time of the epidermal growth factor can be remarkably prolonged. In addition, a stable repairing microenvironment can be formed on the surface of the endometrium, and the endometrium injury repairing effect is remarkably improved.

The invention discloses a radionuclide labeled molecular probe for detecting collagen structure denaturation and a preparation method and application thereof, and relates to the technical field of biology. The structural general formula of the radionuclide labeled molecular probe disclosed by the invention is as follows: K (chelating agent-nuclide)-K-Linker-CHP, wherein K (chelating agent-nuclide) is a lysine residue labeled by a side chain amino coupling chelating agent and a radionuclide; the Linker is a connection joint; cHP is a collagen hybrid peptide with a polypeptide sequence of (GfO) n or (GPO) n. The probe has excellent definition and signal-to-noise ratio, not only can detect pancreatic ductal adenocarcinoma in a pancreatic cancer model, but also can sensitively detect precancerous lesions (such as pancreatic intraepithelial neoplasia lesions) of the pancreatic ductal adenocarcinoma and pulmonary fibrosis lesions in a bleomycin pulmonary fibrosis model. And the kit has important significance on early detection of pancreatic duct adenocarcinoma and reflection of dynamic change of ECM remodeling.

The invention belongs to the technical field of biomedicine, and discloses application of histone lactic acid modification as a target spot in preparation of a medicine for preventing or treating chronic obstructive pulmonary diseases, in particular to lactic acid modification on 18th lysine residues of histone 3, and the expression level of ATM protein in airway epithelial cells is up-regulated through the histone lactic acid modification, so that the chronic obstructive pulmonary diseases can be prevented or treated. The expression of cell senescence key genes is promoted, so that the senescence phenotype of airway epithelial cells is aggravated, and the airway epithelial cells participate in the disease process of mediating the chronic obstructive pulmonary disease. The discovery provides a new therapeutic target for the chronic obstructive pulmonary disease.

The invention belongs to the technical field of biological medicines, and particularly discloses an insulin-like growth factor-1-linker polypeptide-collagen, and the linker polypeptide has an amino acid sequence as shown in SEQ ID No.1. The N end of the designed and synthesized linker polypeptide simulates an IGF-1 receptor structure and can be combined with IGF-1, the C end of the linker polypeptide is rich in lysine residues and can be covalently cross-linked to collagen through glutamine transaminase, the attachment time of the IGF-1 in endometrium is prolonged, and endometrium thickening and endometrium injury repair are effectively promoted. The protein solution for promoting endometrial injury repair provided by the invention can form a stable repair microenvironment on the surface of the endometrial, promote the number recovery of endometrial glands with intrauterine adhesion, reduce the fibrosis ratio and promote the thickening of thin endometrial, has the advantages of high histocompatibility, simplicity in preparation, obvious improvement effect and the like, and can be used for preparing a medicine for treating endometrial injury. The method has no potential toxic influence on cells and has a good clinical application prospect.

Described herein is a polypeptide comprising an immunoglobulin chain variable domain comprising three complementarity determining regions (CDR1-CDR3) and four framework regions, wherein: (a) at least one lysine residue in CDR1, CDR2 and / or CDR3 has been substituted with at least one histidine residue, and / or (b) at least one arginine residue in CDR1, CDR2 and / or CDR3 has been substituted with at least one histidine residue. The polypeptides of this disclosure possess increased intestinal stability relative to a corresponding polypeptide not having the histidine substitutions.

The present disclosure relates to novel antibodies binding to GPC3 or antigen-binding fragments thereof. These anti-GPC3 antibodies or fragments thereof preferably don't comprise lysine residues within their CDRs and are therefore especially suitable for conjugation. The present disclosure further relates to targeted radionuclide conjugates such as targeted actinium-225 conjugates (TACs). Preferred are TACs of formula (I) comprising the anti-GPC3 antibodies according to the present disclosure or fragments thereof. Said antibodies or antigen binding fragments thereof, and / or said antibody conjugates and / or said TACs are useful in diagnostics and / or therapy, preferably in therapy, more preferably in treating cancer, most preferably in treating hepatocellular carcinoma (HCC). Provided are pharmaceutical compositions and kits with instructions for use comprising these antibodies, functional fragments and conjugates. The disclosure further provides methods and tools to generate these antibodies, functional fragments and conjugates.

Described are peptides including a membrane translocation domain having one or more cell penetrating peptide motifs, and a cargo moiety linked to the membrane translocation domain, wherein the cargo moiety includes a plant bioactive moiety. The at least one cell penetrating peptide motif is from 3 to 10 amino acid residues in length and has at least three arginine and / or lysine residues; or the at least one cell penetrating peptide motif is from 3 to 10 amino acid residues in length and has at least two arginine and / or lysine residues and at least one other cell penetrating peptide motif is from 2 to 8 amino acid residues in length and has at least two hydrophobic residues. Also described are methods of delivering a cargo moiety into a plant cell comprising contacting the plant cell with the peptide as disclosed herein.

The present invention relates to a method for generating an antibody-payload conjugate by means of a transglutaminase. The method comprises a step of conjugating a linker comprising the structure (shown in N→C direction) (Sp1)-K-(Sp2)-B-(Sp3) or (Sp1)-B-(Sp2)-K-(Sp3) to a Gln residue comprised in an antibody, wherein (Sp1) is a chemical spacer or is absent; (Sp2) is a chemical spacer or is absent; (Sp3) is a chemical spacer or is absent; K is lysine or a lysine derivative or a lysine mimetic; B is a linking moiety or a payload; wherein the linker is conjugated to the Gln residue comprised in the antibody via a primary amine comprised in the side chain of the lysine residue, the lysine derivative or the lysine mimetic; and wherein the antibody is contacted with less than 80 molar equivalents of the linker. Further, the invention relates to antibody-linker conjugates, antibody-drug conjugates and linker constructs comprising a lysine residue.

Disclosed is a method for improving affinity of an antibody for an antigen, the method comprising: in the antibody, changing at least 3 amino acid residues of framework region 3 (FR3) as defined by Kabat method to arginine residues or lysine residues, thereby improving affinity of an antibody for an antigen as compared with that of an antibody before said at least 3 amino acid residues are changed to arginine residues or lysine residues, wherein said at least 3 amino acid residues comprise at least 3 selected from the group consisting of amino acid residues at positions 68, 70, 72, 74, 75, 77, 79, 81, 82A, 82B, 83, 84, 85 and 87 of a heavy chain as defined by the Kabat method.

Hybrid peptide compounds having a modified lysine residue are described herein.

The invention belongs to the technical field of biological medicine, and provides a multifunctional fusion peptide modified 3D printing Ti implant constructed by a fusion peptide platform and a preparation method and application thereof. The antibacterial peptide KR-12 and the adhesion peptide GFOGER are simultaneously loaded on the surface of the 3D printing titanium implant through the specific targeting peptide minTBP-1. The sequence of the fusion peptide platform is divided into four main components: bioactive polypeptide sequences KR-12 and GFOGER; a connection unit (Linker); a lysine residue; a specific anchoring group minTBP-1; the composite material has specific loading and slow release capabilities, and utilizes synergistic antibacterial and osteogenesis functions to cope with continuous challenges of implant infection and insufficient osseointegration in biomedical equipment. Meanwhile, sterilization and bone regeneration promotion are achieved, and the method is of great importance to bone healing and enhancement of bone combination around the implant. In addition to the antibacterial effect, the synergistic effect of the antibacterial peptide KR-12 and the adhesive peptide GFOGER can significantly promote osteogenesis of the BMSCs.

The invention relates to a protein consisting of an amino acid sequence in which at least one modification selected from the group consisting of the following [1] to [7] is introduced in the amino acid sequence represented by SEQ ID NO: 1: [1] a modification in which the amino acid residue at a position 103 is substituted with a lysine residue, [2] a modification in which the amino acid residue at a position 76 is substituted with a cysteine residue, [3] a modification in which the amino acid residue at a position 144 is substituted with a cysteine residue, [4] a modification in which the amino acid residue at a position 134 is substituted with a glycine residue, [5] a modification in which the amino acid residue at a position 222 is substituted with a methionine residue, [6] a modification in which the amino acid residue at a position 73 is substituted with a glutamine residue, and [7] a modification in which the amino acid residue at a position 203 is substituted with a threonine residue.

The application provides a glutarylation site prediction method and device based on a double-generator WGAN-GP, which comprises the following steps: acquiring glutarylated protein data, taking a lysine residue as a window center, setting a fixed window size to cut a sequence fragment, taking glutarylated samples as positive samples, and taking non-glutarylated samples as unlabeled samples; establishing and training a reliable non-glutarylated site selection model, the reliable non-glutarylated site selection model adopts WGAN-GP, and comprises two generators and one discriminator; selecting reliable negative samples from the unlabeled samples by using the discriminator in the reliable non-glutarylated site selection model; and predicting glutarylated sites based on glutarylated site and reliable non-glutarylated site information to obtain the prediction results of the glutarylated sites and the non-glutarylated sites. The application can improve the purity of the non-glutarylated sites used for model training, and improve the accuracy and reliability of the glutarylated site prediction.

The present invention addresses the problem of providing an enzyme agent containing a novel aminopeptidase that exhibits substrate specificity different from that of conventional aminopeptidase. The present invention relates to an enzyme agent comprising, as an active ingredient, aminopeptidase comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 8 or an amino acid sequence equivalent thereto. Furthermore, the present invention relates to an enzyme agent which contains, as an active ingredient, an aminopeptidase that is derived from Aspergillus nidulans or Aspergillus oryzae and has the following physicochemical properties. (1) the optimum temperature is about 50 DEG C; and (2) the optimum pH is about 7-8. And (3) primer specificity: the primer has the highest specificity on L-alanine residues or L-lysine residues.

Novel hybrid polynucleotide mRNA (or DNA that encodes the mRNA) has one or more antigens and a sequence that can trigger the cellular Ribosome Quality Control (RQC) mechanism in a cell. The polynucleotide will thus have a triggering sequence, usually a sequence of AAA codons (lysine residues) which stalls translation by the ribosome after the synthesis of the antigenic peptide. This can result in the encoded antigen being presented on MHC-I to enhance an immune response.

The present disclosure provides a carrier peptide fragment with excellent cell membrane permeability. The carrier peptide fragment disclosed herein includes the following amino acid sequence set forth in SEQ ID No.: 1: KKRTLRKSNRKKR, and a lysine residue at a 12th position from an N-terminus of the amino acid sequence is a D-form, and the other amino acid residues are L-forms.

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.

The present invention provides a latex microsphere conjugate or a fluorescent microsphere conjugate, comprising an antibody and a conjugate moiety, wherein 1-27 amino acid residues are chimerically inserted after the C-terminal lysine residue of the heavy chain of the antibody. The conjugate has high activity or high sensitivity.

The invention belongs to the technical field of biological medicine, and particularly relates to a marker for diagnosis or / and prognosis analysis of lung cancer and application of the marker. Researches find that acetylation modification of lysine residues at the 375th site of JMJD6 protein is related to lung cancer, the acetylation modification level of the JMJD6 K375 site in cancer tissue of a lung cancer patient is remarkably lower than that of paracancerous normal tissue, and the acetylation modification level of the JMJD6 K375 site is remarkably related to prognosis of the lung cancer patient. Patients with increased acetylation modification level of the K375 site of the JMJD6 have better total lifetime than patients with low acetylation modification level of the K375 site of the JMJD6; therefore, JMJD6 K375 site acetylation modification can be used for auxiliary diagnosis and prognosis prediction of lung cancer, also can be used as a lung cancer drug action target, is used for screening or preparing drugs for treating lung cancer and / or improving prognosis of lung cancer patients, and has important significance for clinical auxiliary diagnosis and prognosis prediction of lung cancer.

The present invention provides antibody compounds that contain a substitution of cysteine for the reactive lysine residue (lysine 93 by Kabat numbering) in the hydrophobic cleft (38C2_Cys). The invention also provides antibody drug conjugate compounds (ADCs) that contain cargo moieties that are site-specifically conjugated to the engineered cysteine residue in the 38C2_Cys variant antibody. Further provided in the invention are therapeutic applications of the compounds.

Methods are disclosed for producing a polypeptide comprising an amino acid sequence including a lysine residue susceptible to hydroxylation, and / or including a proline residue susceptible to hydroxylation, comprising culturing cells comprising nucleic acid for expressing the polypeptide for the majority of the period of culture in cell culture medium having an Fe ion concentration of less than 60 µM.

This invention relates to the field of anti-aging drug technology, specifically to the application of small molecule compounds in the preparation of anti-aging drugs. These small molecule compounds competitively block the interaction between KDM6A and the vacuolar ATPase V0 domain subunit ATP6V0C by targeting a specific small molecule binding pocket of the histone demethylase KDM6A, thereby inhibiting the demethylation activity of KDM6A on lysine residue 36 of ATP6V0C. These small molecule compounds can effectively downregulate aging-related β-galactosidase activity, improve cell cycle arrest, and reverse the senescent phenotype of nerve cells induced by the environmental pollutant GenX, making them particularly suitable for combating premature aging of nerve cells induced by perfluorinated and polyfluoroalkyl compounds such as GenX. This technical solution can solve the technical problem of the lack of drugs with clearly defined components, a clear mechanism of action, stable efficacy, and the ability to specifically alleviate aging in existing technologies, and has ideal prospects for widespread application.

The invention relates to an immobilization method and application of an alpha-amino acid ester acyltransferase immobilized enzyme, and belongs to the technical field of biological enzymes. In order to solve the problems of poor immobilization and difficulty in removing miscellaneous enzymes in the prior art, the invention provides an immobilization method of an alpha-amino acid ester acyltransferase immobilized enzyme, which comprises the following steps: under the catalytic action of a TG enzyme, carrying out enzyme protein cross-linking immobilization reaction on alpha-amino acid ester acyltransferase containing a plurality of glutamine residues and gelatin to obtain the alpha-amino acid ester acyltransferase immobilized enzyme. The immobilized alpha-amino acid ester acyltransferase immobilized enzyme is obtained. According to the present invention, the TG enzyme can well catalyze the glutamine residue and the lysine residue of the target protein to form the cross-linking reaction, and other miscellaneous enzymes are distinguished so as to avoid the reaction of the miscellaneous enzymes and gelatin, such that the good selectivity and the good specificity are provided, and the purification purpose can be easily achieved.

The present specification reports a polypeptide-linker-nucleic acid conjugate, wherein the linker comprises a 3-aminopropanamide unit, a 2,6-diaminohexanoic acid amide unit, and a 1,4,5,5a,6,6a,7,8-octahydrocyclopropa[5,6]cycloocta[1,2-d]-1,2,3-triazole unit, the polypeptide comprises a C-terminal lysine residue, the nucleic acid comprises an oxygen atom at the 5' or 3' end linked to a phosphorus atom in oxidation state V, and the 3-amino group of the 3-aminopropanamide unit and the carboxy functional group of the lysine residue of the polypeptide are linked by / form an amide bond, and the 3-aminopropanamide unit is linked to the carboxy functional group of the lysine residue of the polypeptide. The carboxyl functional group at position 1 and the alpha amino group of the 2,6-diaminohexanoic acid amide unit are linked by / form an amide bond, the 6-amino group of the 2,6-diaminohexanoic acid amide unit is the nitrogen of the 1,2,3-triazole element of the 1,4,5,5a,6,6a,7,8-octahydrocyclopropa[5,6]cycloocta[1,2-d]-1,2,3-triazole unit, and the oxygen linked to the phosphorus atom of the nucleic acid is covalently linked to the cyclopropane element of the 1,4,5,5a,6,6a,7,8-octahydrocyclopropa[5,6]cycloocta[1,2-d]-1,2,3-triazole unit.

The present disclosure provides an enzyme electrode or the like in which an enzyme is immobilized by more appropriate binding. An enzyme electrode according to the present disclosure is provided with an electrode and a modified protein having an amino acid sequence in which at least one lysine residue in a protein that is a reductase or a dehydrogenase is replaced with another amino acid residue, wherein the modified protein is immobilized on the surface of the electrode.

The invention provides a mutant of soybean lipoxygenase LOX2 and application of the mutant in creation of fishy-smell-free soybeans, the mutant is based on a parent amino acid sequence of SEQ ID NO.1, succinylation modification is introduced into lysine residues at the 257th site, the 263rd site and the 472th site, the catalytic efficiency of LOX2 is reduced, oxidation of polyunsaturated fatty acid is reduced, and the yield of the soybean lipoxygenase LOX2 is increased. And the fishy-smell-free soybeans are effectively prepared. Compared with a wild type, the catalytic efficiency is reduced by 15.62%, and a new basis is provided for food industrial application. In addition, molecular transformation is realized through a grafting breeding technology, the soybean quality is improved, the production cost is remarkably reduced, and the method has important significance on soybean variety improvement and grease quality improvement.

Described are peptides comprising a membrane translocation domain having one or more cell penetrating peptide motifs and a cargo moiety linked to the membrane translocation domain, wherein the cargo moiety comprises a plant bioactive moiety. The at least one cell penetrating peptide motif has a length of 3 to 10 amino acid residues and has at least three arginine and / or lysine residues; or the at least one cell penetrating peptide motif has a length of from 3 to 10 amino acid residues and has at least two arginine and / or lysine residues and the at least one other cell penetrating peptide motif has a length of from 2 to 8 amino acid residues and has at least two hydrophobic residues. Also described are methods of delivering cargo moieties into plant cells, comprising contacting the plant cells with the peptides disclosed herein.

Provided is a polypeptide for localizing a fusion protein of a protein and the polypeptide in an exosome by being added to the C-terminus of the protein, wherein, in the polypeptide, the N-terminal amino acid sequence includes an amino acid sequence represented by formula 1 and the C-terminal amino acid sequence includes an amino acid sequence represented by formula 2.　Formula 1: K-X11-X12-X13-K, wherein X11 and X12 each independently represent any one amino acid residue selected from the group consisting of an L-lysine residue, an L-arginine residue, an L-serine residue, an L-threonine residue, and an aliphatic amino acid residue, and X13 represents an L-lysine residue or an L-arginine residue.　Formula 2: C-X21-X22-X23, wherein X21 and X22 each independently represent an aliphatic amino acid residue, and X23 represents an amino acid residue.

The invention belongs to the field of biological medicine, and particularly relates to PGK1 K6 site succinylation modification and application. Experiments show that the 6th lysine of the PGK1 protein has succinylation modification (PGK1 K6su), and the existence of the succinylation modification at the 6th lysine is confirmed through immunoprecipitation experiments; cell function experiments prove that the PGK1 K6su enhances lung cancer cell migration and multiplication capacity and promotes lung cancer progression. A small molecule compound diammonium glycyrrhizinate aiming at the PGK1 K6 site is further obtained through computer-assisted screening, and subsequent experiments find that the compound can inhibit proliferation and migration of lung cancer cells by reducing the succinylation modification level of the lung cancer cells PGK1 K6.