147 results about "Amino acid replacement" patented technology

Provided is an antibacterial peptide having an amino acid sequence X1KRFKKFFX2KLKKWV-NH2, wherein X1 is selected from any one or of amino acids A, C, D, E, F, G, H, K, L, N, M, P, Q, R, S, I, V, W, Y, and T or is absent; and X2 is an amino acid having an aromatic side chain or an amino acid having an alkaline side chain. In view of defects such as poor gastrointestinal fluid stability of antibacterial peptides in the prior art, a brand-new sequence design scheme and preparation method for an antibacterial peptide are provided. By means of a complete or partial D-amino acid substitution or structural derivatization of a peptide sequence, a series of antimicrobial peptides having stronger antibacterial activity and gastrointestinal stability as compared with the prior art are obtained, such that the antibacterial peptides have a wider application range and higher development potential value.

The invention discloses an anti-TP53 mutation T cell receptor and application thereof, the T cell receptor comprises specific alpha chain and beta chain variable domains, and the complementary determining region (CDR) sequence is shown as SEQ ID NO: 9-14. The TCR has the core advantage that the TCR has excellent broad-spectrum recognition capability, can target six different amino acid substitutions (A, G, I, N, S and T) at the R249 site, and effectively deals with tumor heterogeneity and mutation difference between patients. Aiming at high-frequency HLA-B * 07: 02 alleles in people, the TCR lays a foundation for developing TCR-T cell therapy covering a wide range of people, and has great clinical application value and market potential in treatment of various solid tumors carrying TP53 R249 hotspot mutation, such as liver cancer.

The invention relates to the technical field of antibacterial drugs, in particular to an antibacterial peptide which has an amino acid sequence X1KRFKKFFX2KLKKWV-NH2, in which X1 is selected from any one or deletion of amino acids A, C, D, E, F, G, H, K, L, N, M, P, Q, R, S, I, V, W, Y and T; and X2 represents an amino acid having an aromatic side chain or an amino acid having a basic side chain. Aiming at the defects of poor gastrointestinal fluid stability and the like of the antibacterial peptide in the prior art, the invention provides a brand new antibacterial peptide sequence design scheme and a preparation method thereof, and the peptide sequence is subjected to full D-type amino acid or partial D-type amino acid replacement or structure derivation; compared with the prior art, a series of antibacterial peptides with higher antibacterial activity and gastrointestinal fluid stability are obtained, so that the antibacterial peptides have wider application range and higher potential development value.

The invention relates to the technical field of genetic engineering, in particular to Encapsulin fusion protein for expressing foot and mouth disease virus epitopes and application of the Encapsulin fusion protein in preparation of subunit vaccines. The invention discovers that different serotypes of foot-and-mouth disease virus antigen epitopes are inserted among the 62nd to 63rd positions, the 124 to 125th positions, the 138 to 139th positions and the 239th to 240th positions of amino acids of an Encapsulin protein fragment subjected to amino acid sequence modification, and / or the 62nd to 63rd positions, the 124 to 125th positions, the 138 to 139th positions and the 239th to 240th positions of amino acids are replaced by the different serotypes of foot-and-mouth disease virus antigen epitopes; efficient and soluble expression of a target antigen in escherichia coli can be realized, and protein cage nano antigen particles are successfully self-assembled; the protein nano antigen particle can induce a widely neutralized foot-and-mouth disease virus antibody, improves the immune efficacy, and has the potential of becoming a broad-spectrum multivalent vaccine for foot-and-mouth disease.

The present invention relates to a compound binding to an endogenous receptor, said compound comprising (i) an oligopeptide comprising a dipeptide with Trp being the C-terminal amino acid of said dipeptide, wherein said Trp is replaced with an α-amino acid Xaa2, whereby the stability in serum or plasma of the peptide bond connecting Xaa2 to the N-terminally adjacent amino acid is increased as compared to the peptide bond connecting Trp to the N-terminally adjacent amino acid in an otherwise identical compound; and (ii) a moiety capable of generating therapeutically effective radiation, said moiety being covalently bound to said oligopeptide.

The present invention is related to the field of protein engineering technology which increases the enzymatic activity and thermal stability of human hyaluronidase which is an enzyme that hydrolyzes hyaluronic acid; and more particularly to hyaluronidase PH20 variants or fragments thereof, which comprise one or more amino acid residue substitutions in the region corresponding to the alpha-helix region and / or its linker region in the amino acid sequence of wild-type PH20 of SEQ ID NO: 1 and in which one or more amino acid residues at the N-terminus and / or the C-terminus are selectively truncated additionally.Specifically, the present invention relates to PH20 variants or fragments thereof, which comprise one or more amino acid residue substitutions selected from the group consisting of T341A, T341C, T341G, S343E, M345T, K349E, L353A, L354I, N356E and I361T in wild-type PH20 having the amino acid sequence of SEQ ID NO: 1, and additionally comprise the substitution of amino acids located in the alpha-helix 8 region and / or a linker region between alpha-helix 7 and alpha-helix 8 in the amino acid sequence of wild-type PH20, and in which portion(s) of amino acids located at the N-terminal and C-terminal regions are deleted.

A CVB virus expression vector comprising a PIV5 W3A viral genome comprising a mutation at amino acid residue S157 or S156 of the P / V gene and a deletion of the small hydrophobic (SH) gene of the PIV5 W3A viral genome, wherein the amino acid substitution at amino acid residue S157 or S156 comprises a substitution of serine (S) with phenylalanine (F) or asparagine (N), and the SH gene has a deletion of the SH open reading frame or the entire SH gene transcription unit. The CVB virus expression vector expresses a heterologous polypeptide, including SARS-CoV-2 spike (S), and / or nucleocapsid (N) and / or membrane (M) proteins, RSV fusion protein (F), or other antigens.

The invention relates to the technical field of genetic engineering, in particular to a self-assembled protein cage nanoparticle epitope insertion site and application thereof in vaccine preparation. It is found that a foot-and-mouth disease virus antigen epitope is inserted between the 124 -125 amino acid of an Encapsulin protein fragment subjected to amino acid sequence modification, and / or the 124 -125 amino acid is replaced with the foot-and-mouth disease virus antigen epitope, efficient and soluble expression of a target antigen in escherichia coli can be achieved, and protein cage nano antigen particles are successfully self-assembled; the protein nano antigen particle can induce a widely neutralized anti-foot-and-mouth disease virus antibody, improves the immune efficacy, and has the potential of becoming a foot-and-mouth disease vaccine.

To provide T7 RNA polymerase variants.SOLUTION: The present invention provides engineered T7 RNA polymerase variants and a composition thereof. The variants have been devised in order to selectively incorporate a symmetrically capped GTP analogue exceeding GTP in starting in-vitro transcription. The present invention further provides a method for using a variant provided in the specification. The present invention further provides a use of a composition provided in the specification. The engineered RNA polymerase variant can include at least one substitution or substitution set in a polypeptide sequence.SELECTED DRAWING: None

A variant polypeptide of xylanase, and a fusion protein and an enzyme composition comprising the variant polypeptide, a recombinant host cell for production of the variant polypeptide, methods for using it and its use, is disclosed comprising an amino acid sequence having at least 79%, but less than 100% amino acid sequence identity with amino acids 1-191 of SEQ ID NO: 1, wherein the amino acid sequence has xylanase activity, at least one disulfide bridge between two Cys residues in the 1-191 amino acid region, and an amino acid substitution at the position 23 or 28, or at the positions 23 and 28, the positions corresponding to the positions 23 and 28 of the SEQ ID NO: 1.

The invention relates to the technical field of biological medicines, and provides a polypeptide targeting a BRAF dimer and an application of the polypeptide in tumor resistance, the polypeptide takes a straight-chain peptide TRHVNILLFM-OH as a peptide chain template, the straight-chain peptide is constructed through specific amino acid replacement, the C terminal is gradually truncated and cyclized to construct a cyclic peptide, and a specific sequence is coupled to develop a composite peptide strategy for modification, so that the polypeptide targeting the BRAF dimer is obtained. The cyclic peptide CBF-2, the cyclic peptide CBF-2-2 and the cyclic peptide SCBF-2-2 are obtained. Experiments prove that the polypeptide can effectively inhibit proliferation and invasion of tumor cells; the serum protein has high stability and excellent cell penetrating capability, and can penetrate through a cell membrane to enter cytoplasm, so that target protein in cells can be better targeted to exert biological functions of the target protein. Therefore, the multi-functional composite peptide can be developed through a polypeptide modification strategy, the membrane permeability and the stability of the multi-functional composite peptide are improved, the binding force of the multi-functional composite peptide and the BRAF protein is further improved, and the effects of inhibiting proliferation of tumor cells and resisting invasion are achieved at the same time.

Disclosed are compositions and methods for engineered DLL4 proteins. In one aspect, disclosed herein are engineered DLL4 proteins comprising a conservative amino acid substitution at a residue corresponding to residues 28, 107, 143, 194, and 206 as set forth in SEQ ID NO: 1 and further comprising at least one conservative amino acid substitution at residues 256, 257, 271, 280, 301, and 305 as set forth in SEQ ID NO: 1.

There is provided a mutant KLF protein that can induce reprogramming of a somatic cell at a higher efficiency than a KLF protein having a natural amino acid sequence. There is also provided a method for efficiently producing an iPS cell by using the mutant KLF protein. There is provided a mutant KLF protein having an amino acid substitution, or a peptide fragment thereof containing the amino acid substitution.

The disclosure provides Fc polypeptides wherein the Fc domain comprises at least one amino acid substitution that reduces binding affinity to an Fc receptor and / or effector function comprising one or more, two or more, three or more, four or more, or all five amino acid substitutions selected from L234A, L235A, G237A, K322A, and P329G, wherein the residues are numbered according to the EU index, preferably wherein the Fc polypeptide is an antibody. In some embodiments, the antibody is an anti-GIP antibody. In some embodiments, the antibody further comprises the three M252Y, S254T and T256E substitutions or the two M428L and N434S substitutions, which extend the half-life of the antibody.

To provide AAV having modified transduction ability, the AAV including in its structure, various kinds of transducing genes including a clinically important transducing gene for a patient who requires a transducing gene.SOLUTION: There are provided: an isolation modification VP1 protein of an adeno-associated virus serotype 5 (AAV5) capsid, including one or more amino acid replacements for improving transduction efficiency, relative to VP1 protein of a wild type AAV5 capsid; and capsid and vector based on the isolation modification VP1 protein.SELECTED DRAWING: None

The invention provides a novel herbicide-resistant mutation efficiently created by editing a rice genome targeted G-to-T basic group. Specifically, the invention provides a separated herbicide resistant polypeptide, and the herbicide resistant polypeptide is a mutant ALS1 polypeptide, the mutant ALS1 polypeptide is mutated at the 171st amino acid, corresponding to SEQ ID NO.1, of the wild ALS1 polypeptide, and proline (P) at the 171st position is mutated into one or more amino acids selected from the following groups: threonine (T), histidine (H), asparagine (N) and arginine (R). According to the invention, it is found for the first time that a guanine base editor is used for editing the wild ALS1 polypeptide in a plant; efficient G-to-T base editing can be achieved, multiple amino acid replacement types which are not reported before are created, and partial mutation types can greatly improve the tolerance of plant herbicides.

To provide a modified tyrosine phenol lyase having improved activity for catalyzing a reaction (tyrosine cleavage reaction) for producing phenol from tyrosine.SOLUTION: Provided is a modified tyrosine phenol-lyase comprising an amino acid sequence in which one or more amino acid substitutions are introduced into an amino acid sequence of a wild-type tyrosine phenol-lyase, wherein an activity of catalyzing phenol production from tyrosine is improved compared to the wild-type tyrosine phenol-lyase, wherein the modified tyrosine phenol-lyase has amino acid substitutions at any one or more positions selected from positions corresponding to positions 25, 75, 144, 391, 419, and 456 of the amino acid sequence of SEQ ID NO: SELECTED DRAWING: Figure 1

The application discloses a method for constructing a CRBN gene humanized mouse model, which comprises replacing a knockout region of a mouse CRBN gene with a knock-in region of a human CRBN gene, so that the CRBN gene humanized mouse model is constructed, and the CRBN gene of the CRBN gene humanized mouse model is subjected to amino acid substitution of S369C, V380E, I391V and E431D. The application replaces a key functional domain of a mouse endogenous CRBN gene with a corresponding sequence of a human CRBN gene, so that the mouse can express a functional human CRBN protein, thereby solving the problem of lack of sensitivity of a wild-type mouse to a CRBN-dependent drug. The model provides an ideal preclinical experimental platform for studying the efficacy, toxicity and mechanism of action of a CRBN-related drug.

Provided is a parent phytase variant, which relates to the technical field of protein engineering. The variant, relative to the parent phytase thereof, has one or more amino acid substitutions at positions corresponding to positions 295, 349, and 374 of SEQ ID NO: 1. Compared to the parent phytase, the variant has increased thermal stability.

This invention relates to the field of biomedicine, specifically providing a mutant thymosin α1 polypeptide and its applications. The mutant differs from natural thymosin α1 by substituting at least one amino acid at positions 15, 21, and 27, with preferred mutations including D15M, E21W, and E27R. Amino acid substitutions at these sites significantly improve the structural stability and in vivo pharmacokinetic properties of thymosin α1. Experimental results show that, while maintaining the main secondary structural features and overall thermal stability without significant degradation, the mutant improves serum stability and in vivo pharmacokinetic properties, exhibiting superior in vivo half-life and antitumor activity. This invention also provides nucleic acid molecules encoding the mutant, expression vectors, host cells, and pharmaceutical compositions containing the mutant, which can be used for the treatment of tumors, viral infections, and immune-related diseases.

The invention relates to variants of the alpha subunit of interleukin-2 receptor (IL2R) and interleukin-2 (IL2). In one embodiment, the IL2 variants described herein have amino acid substitutions at the region of IL2 that contacts the alpha (α) subunit of the heterotrimeric IL2 receptor complex, IL2Rαβγ, reducing its ability to bind and activate the heterotrimeric receptor complex. Conversely, the corresponding IL2Rα variants described herein have amino acid substitutions compensating for such reduced ability of IL2 variants to bind to and activate IL2Rαβγ, preferably at amino acid residues contacted by IL2 amino acid residues that are substituted in the IL2 variants described herein.

The application discloses a kind of low-toxicity broad-spectrum antibacterial peptide with WW as symmetry center, the antibacterial peptide is that WK is repeated twice and symmetrically distributed in two sides, and WW is used as symmetry center, obtain antibacterial peptide WKWKWWKWKW-NH2 (N2W2), then the tryptophan of C terminal and N terminal of N2W2 is replaced by leucine and / or isoleucine;The antibacterial peptide can basically maintain the excellent antibacterial activity of parent peptide, and their hemolytic activity is greatly reduced, and the safety is improved. The antibacterial activity of IL-N2W2 is highest, but the stability needs to be improved, so D-type amino acid replacement is carried out on IL-N2W2 to obtain D-IL-N2W2. D-IL-N2W2 maintains the high antibacterial activity and low toxicity of IL-N2W2, and can still completely inhibit bacterial growth after incubation with high-concentration trypsin or chymotrypsin, has very great potential in relieving antibiotic resistance, and has good application prospect in preparing clinical antibacterial drugs.

To provide more active hyperactive transposons and transposases.SOLUTION: The present invention relates to a polypeptide comprising a piggyBac transposase or a fragment or a derivative thereof having a transposase function comprising at least one amino acid substitution. Further, the present invention relates to a transposable element comprising a piggyBac or piggyBac-like left repeat sequence and left internal repeat sequence, where the left internal repeat sequence comprises at least one nucleotide modification. Furthermore, the present invention relates to a kit comprising the transposase and / or transposable element. In addition, the present invention relates to a targeting system comprising the transposase and / or transposable element.SELECTED DRAWING: None

The present invention discloses a novel antimicrobial peptide and its application. The present invention optimizes the structure of Epi-1, cuts off the non-α regions at both ends, and obtains a target antimicrobial peptide with a 16-amino acid sequence by replacing individual amino acids, thereby obtaining a novel antimicrobial polypeptide F-3 with a shorter sequence, higher antimicrobial activity, and better biocompatibility. A nucleic acid molecule encoding the antimicrobial peptide and an expression vector or recombinant cell containing the nucleic acid molecule are also provided. In vitro verification found that compared with the parent peptide, the derived peptide F-3 has higher antimicrobial activity or a higher bactericidal rate, and the minimum inhibitory concentration of F-3 is less than that of the parent peptide Epi-1; F-3 can also effectively inhibit or eliminate the formation of Enterococcus faecalis biofilm, and has low toxicity and good biocompatibility, and can be used to prepare drugs for preventing and treating diseases caused by Enterococcus faecalis infection; and the shorter amino acid sequence reduces the synthesis cost, and has good application prospects.

The invention relates to proteases exhibiting proteolytic activity and comprising an amino acid sequence that, over its total length, corresponds to the amino acid sequence specified in SEQ ID NO:1 by at least 70% and increasingly preferably by at least 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94.5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5% and 98% is identical, wherein the protease, with reference to the numbering according to SEQ ID NO:1, has at least one amino acid substitution at at least one of the positions corresponding to positions 97, 3, 99, 127 and 211, which is selected from the group consisting of N97E, R99E, R99I, R99N, R99V, R99T, D127E and M211C. Such proteases are suitable for use in washing and cleaning agents, in particular liquid textile detergents, and exhibit improved cleaning performance compared to a reference protease.The invention further relates to the use of these proteases and processes in which they are used, as well as washing and cleaning agents containing them, in particular liquid textile detergents.

The invention relates to the technical field of genetic engineering, in particular to identification of a new insertion site of a self-assembled protein cage nanoparticle antigen epitope and application of the new insertion site in vaccine preparation. It is found that a foot-and-mouth disease virus antigen epitope is inserted between 62nd-63rd amino acids of an Encapsulin protein fragment after amino acid sequence modification, and / or the 62nd-63rd amino acids are replaced with the foot-and-mouth disease virus antigen epitope, efficient and soluble expression of a target antigen in escherichia coli can be achieved, and protein cage nano antigen particles are successfully self-assembled; the protein nano antigen particle can induce a widely neutralized anti-foot-and-mouth disease virus antibody, improves the immune efficacy, and has the potential of becoming a foot-and-mouth disease vaccine.

Provided herein are variant IgG4 Fc domains comprising amino acid substitutions that decrease self-interaction of a polypeptide and / or decrease aggregation.

This application relates to the fields of gene therapy and molecular biology. More specifically, the present invention relates to an isolated altered VP1 protein of adeno-associated virus serotype 5 (AAV5) capsid comprising one or more amino acid substitutions as compared to the VP1 protein of wild-type AAV5 capsid, which increase transduction efficiency, as well as to a capsid and a vector based thereon.

Belongs to the field of biological medicine, and relates to a polypeptide active molecule with prolonged half-life period and improved stability, which increases the half-life period and the stability by replacing L-type amino acid at a specific position with D-type amino acid.

The present application relates to a Cas12 protein having an amino acid sequence set forth in any one of SEQ ID NOs: 1 to 104, or a functional fragment thereof, or having an amino acid sequence set forth in any one of SEQ ID NOs: 1 to 104 with one or more amino acid substitutions, insertions, and / or deletions, and a CRISPR-Cas system comprising the Cas12 protein, and use thereof.