89 results about "Bioconjugation" patented technology

The present disclosure sets forth novel compounds and compositions including heteroaromatic silicon-fluoride-acceptors, which are useful for PET scanning. The present disclosure further includes novel methods of 18F imaging for PET scanning, the methods comprising the preparation of conjugates and bioconjugates of biological ligands of interest with heteroaromatic silicon-fluoride-acceptors. In certain embodiments the invention is practiced in the form of a kit.

Bioconjugates are described comprising alpha-fetoprotein (AFP) linked with a cytotoxin through a disulfide, glutathione-sensitive linker, for cancer treatment. In a preferred embodiment, the bioconjugate is an AFP variant linked with a maytansinoid cytotoxin via the glutathione-sensitive linker so that the bioconjugate comprises either specific high or low ratio of cytotoxins per AFP.

Methods of producing bioconjugates of O-antigen polysaccharides covalently linked to a carrier protein using recombinant host cells are provided. The recombinant host cells used in the methods described herein encode a particular oligosaccharyl transferase enzyme depending on the O-antigen polysaccharide bioconjugate to be produced. The oligosaccharyl transferase enzymes can be PglB oligosaccharyl transferase or variants thereof. Also provided are compositions containing the bioconjugates, and methods of using the bioconjugates and compositions described herein to vaccinate a subject against extra-intestinal pathogenic E. coli. (ExPEC).

To provide a bioconjugate comprising an oligo- or polysaccharide covalently linked to a fusion protein.SOLUTION: The present invention provides a bioconjugate comprising an oligo- or polysaccharide covalently linked to a fusion protein, wherein the fusion protein comprises a ComP protein (ComP) glycosylation tag, wherein the ComP glycosylation tag comprises a cysteine residue conserved in a specific amino acid sequence, and the fusion protein is glycosylated with an oligo- or polysaccharide at a serine residue conserved in a specific amino acid sequence.SELECTED DRAWING: None

A virus conjugate comprising a genetically-modified adeno-associated virus (AAV), wherein the virus is mutated to incorporate an engineered amino acid in a site-specific manner and a genetically-modified protein of interest, wherein the protein is mutated to incorporate an engineered amino acid in a site-specific manner, wherein the engineered amino acids can further comprise orthogonal bioconjugation groups suitable for attachment of a bifunctional linking reagent, whereby the virus and protein are cross-linked via the bifunctional chemical linker reagent to form a virus conjugate is described.

Disclosed are polypeptides that can be used for bioconjugation. The polypeptides have transglutaminase activity, and they can be used to make biomolecule-compound conjugates, for example to conjugate a compound to a specific lysine or glutamine of an antibody.

Disclosed herein, inter alia, are silicon containing detectable compounds and methods of use thereof. In an aspect is provided a monovalent nucleotide or monovalent nucleoside covalently bound to a monovalent form of a compound described herein (e.g., wherein the R13 moiety of a compound described herein has reacted with a bioconjugate reactive group to form a bioconjugate linker thereby covalently bonding the monovalent compound to the monovalent nucleotide or monovalent nucleoside).

A bio-orthogonal cycloaddition reaction is provided, as well as uses in the assembly of TAC-type molecules and the preparation of bioconjugates. A method of conducting a coupling reaction includes providing a first structure comprising a diketone group or a derivative thereof and a second structure capable of providing anionic 2-furanol or a derivative thereof.

The present invention provides a bioconjugation process for preparing a composition of antibody-drug conjugates (ADCs) with improved homogeneity, wherein antibody-drug conjugates (ADCs) having a molar ratio of drug to antibody of 2 (D2) are present at high levels in the composition. In the ADC composition prepared by the method of the present invention, the content of D2 is greater than 64 mol% and the content of D0 + D4 + D6 + D8 is less than 36 mol% based on the total molar amount of D0, D2, D4, D6 and D8.

This invention discloses a selenylamide-based hydrogenation reaction of acetylacetamide compounds and its application in the modification of selenium-containing peptides and proteins, belonging to the fields of organic chemistry and chemical biology. The reaction involves the reaction of a selenium-containing compound with an acetylacetamide compound in a solvent with the addition of an additive. The applications of this reaction include: 1) selective modification and labeling of selenocysteine ​​in peptides and proteins; 2) cyclization reactions of selenium-containing peptides and selenoproteins; and 3) sequential modification of selenium-containing peptides in the presence of cysteine ​​by precise pH control combined with the hydrogen sulfide reaction of acetylacetamide. This reaction has advantages such as mild conditions, simple operation, fast reaction rate, high yield, good stability, and good selectivity. It provides a new and robust approach for the selective modification and labeling of selenium groups in bioconjugations, peptides, and / or proteins, and also provides a new method for the construction of cyclic peptides, offering a powerful tool for the development of selenium-containing peptide drugs.

Provided for herein is a polynucleotide-modified bioconjugate comprising a substrate such as an antibody or bead linked to a conjugate component via a nucleic acid linker. Also provided are methods of making and using such bioconjugates. Conjugation methods for creating the bioconjugate are stable, not chemically harsh, and efficient enough that post-conjugation purification may not be required. Further this disclosure provides for reducing the logistic overheads related to product lines by eliminating the need for many unique linkers per conjugation pair.

The present invention relates to providing more efficient methods of conjugating two or more peptides. For example, the invention provides more efficient methods of producing antibody-drug conjugates. More particularly, the methods can be used to efficiently produce ADCs with at least two unique payloads. One approach involves the use of peptidyl asparaginyl ligases (PALs) for two consecutive ligation reactions at the N-terminal and C-terminal ends of a protein and the other approach involves the use of a chemical protein modification reaction and a PAL-mediated enzymatic ligation reaction, both able to introduce two different payloads to an antibody at specific sites.

The present invention relates to narrow emission dyes, compositions comprising the same, and methods of making and using the same. In particular, the present application provides bacteriochlorin derivatives having narrow band emission. In some embodiments, the bacteriocin derivative is PEGylated. In some embodiments, the bacteriocin derivatives have a high water solubility (e.g., 10 mg / mL or more). In some embodiments, the bacteriocin derivatives are PEGylated and have a high water solubility. The bacteriocin derivatives may comprise a bioconjugatable group for forming a conjugate (e.g., with an antibody or nanoparticle). The bacteriocin derivatives and conjugates thereof are useful for imaging and therapeutic applications. Also provided are methods of synthesizing the bacteriocin derivatives.

In general, disclosed herein are fluorogenic compounds having the structure of Formula (I):Fluorogenic compounds disclosed herein may be useful in methods for visualizing a sample. The method may include conjugating the biomolecule with sample comprising a fluorogenic compound disclosed herein; incubating the biomolecule with the fluorogenic compound for a sufficient time to allow for fluorogenic bioconjugation of the fluorogenic compound; subjecting the fluorogenic compound to an oxidative condition; contacting the fluorogenic compound with a dye; and imaging the fluorogenic compound, thereby determining the fluorescence intensity change of the fluorogenic compound.

The present invention relates to a preparation method of a photoelectrochemical sensor for detecting the transmembrane glycoprotein CD44 on the surface of breast cancer cells. The preparation method is divided into three steps. First, a TiO2 nanoarray is loaded on the surface of FTO conductive glass by a hydrothermal method. Then, a Ag nano-layer is uniformly sputtered on the surface of the TiO2 nanoarray by using a magnetron sputtering technique. Finally, the TiO2-Ag is immersed in a sodium sulfide solution to realize the local sulfidation of Ag to obtain a photoelectric conversion body, a TiO2-Ag-Ag2S nano-composite array. Then, the extraction of the transmembrane glycoprotein CD44 on the surface of breast cancer cells MDA-MB-231 is realized by using the host-guest recognition between hyaluronic acid and the transmembrane glycoprotein CD44 and a DNA strand displacement reaction. Finally, through bioconjugation and covalent bonding, the assembly of the optoelectronic material and the target on the conductive interface is realized. The preparation method of this sensor has stronger controllability compared with other reported methods, especially obtaining a sensing interface with good signal output stability. The scheme and process mentioned in this method have important reference in the fields of material synthesis, photoelectrochemical sensing, cell detection, etc.

A method of attaching an azide moiety to a biomolecule. The method comprises contacting a biomolecule in a solution with an azide and a copper, for a time wherein at least one azide moiety is covalently bonded to the biomolecule to yield an azidylated biomolecule. The copper is copper (I), and can be generated from copper (II) by a reductant. The solution further comprises a copper ligand for reducing degradation of the biomolecule. The azilylated biomolecule can be attached to a reagent comprising an alkyne via a copper-catalyzed azide-alkyne cycloaddition (“CuAAC”) reaction or a strain-promoted alkyne-azide cycloaddition (“SPAAC”) reaction.

Described herein is a general strategy to label recombinant proteins using 5HTP-directed electrochemical conjugation reaction and biomolecular conjugates produced by the covalent electrochemical reactions.

A therapeutic composition is described including a selective soluble TNF-neutralizing bioconjugate for treating TNF-mediated inflammatory disorders. The bioconjugate includes a dominant-negative TNF (DN-TNF) mutein, which contains one or more amino acid substitutions in the TNF receptor interaction domain, trimer interface domain, or both, to reduce receptor binding while enhancing heterotrimer formation with wild-type TNF, thereby neutralizing soluble TNF. The DN-TNF mutein is covalently conjugated to a biocompatible stealth polymer via a hydrolyzed maleimide linker, preventing retro-Michael reaction and polymer dissociation. The composition is formulated as an injectable buffered aqueous solution for subcutaneous, intramuscular, intravitreal, or intravenous administration. Also disclosed are methods for stabilizing the bioconjugate through controlled hydrolysis of the maleimide linker and methods for treating TNF-mediated inflammatory disorders by administering the composition to a subject in need thereof.

The invention relates to an efficient method for synthesizing self-assembling artificial proteins (SAPs) utilizing a catalytic host-guest system. The process involves encapsulating hydrophobic probes with cyclodextrin, performing site-specific protein bioconjugation, and employing a second catalysis cycle for enhanced labeling. SAPs produced through this method are versatile and find applications in therapeutic delivery and diagnostics. The process is simplified, scalable, cost-effective, and environmentally sustainable, addressing the challenges of traditional SAP synthesis. By offering improved yield, functionality, and structural integrity, this invention advances the potential of SAPs in medical and industrial fields.

The present invention provides, among other aspects, functionalized chromophoric polymer dots comprising a hydrophobic core and a hydrophilic cap, and bioconjugates thereof. Also provided are improved methods for preparing functionalized chromophoric polymer dots. Methods for in vivo imaging and molecular labeling are also disclosed.

A bio-conjugation process for preparing a composition of antibody-drug conjugates (ADCs) with improved homogeneity, i.e., a composition of antibody-drug conjugates (ADCs) with high D4 (DAR4) content through simple manipulation is disclosed, wherein the process is performed at room temperature. The resultant composition of ADCs comprises D4 in a content higher than 60 wt%, preferably higher than 65 wt%, on the basis of total weight of D0, D2, D4, D6 and D8.

The present invention relates to a hyaluronic acid hydrogel having a skin wound healing effect by continuously releasing a drug, wherein the hydrogel is prepared by chemically modifying an acrylate group according to the presence or absence of PEG in an epidermal growth factor through an NHS ester amine coupling reaction, which is a type of bioconjugation, and then crosslinking between hyaluronic acid chains is performed through a vitamin B2 derivative (riboflavin phosphate) photoinitiator and blue light irradiation. The present invention relates to a hyaluronic acid hydrogel capable of controlling drug release by means of light by using a photo-cleavable linker, and to a method for preparing a hyaluronic acid (HA)-based hydrogel, and a technique capable of controlling drug release by means of light stimulation.

The present disclosure relates to novel compounds comprising an autohydrolyzing maleimide functional group, salts of these compounds, pharmaceutically acceptable salts of these compounds, methods of making these compounds, and methods of using these compounds for bioconjugation to antibodies. The present disclosure also relates to antibody-drug conjugates with improved stability under physiological conditions. The present disclosure also relates to antibody-drug conjugates comprising an autohydrolyzing maleimide functional group.

The invention relates to an A beta antigen compound based on an AP205 or Lus nanoparticle carrier, a vaccine containing the A beta antigen compound and a preparation method and application of the A beta antigen compound. According to the A beta antigen compound disclosed by the invention, A beta antigen epitope peptide is efficiently loaded on an AP205 / Lus nanoparticle carrier by utilizing a specific SpyCatcher-SpyTag biological coupling system and is self-assembled to form a 180 / 60 polymer spherical structure, so that the A beta antigen epitope peptide is displayed on the surface of the spherical structure to form an ordered and repeated antigen array; therefore, an organism can be stimulated to generate a specific immune response aiming at the A beta protein to the greatest extent, and the immunogenicity is relatively high; the vaccine based on the A beta antigen compound can induce a body to generate a high-titer A beta antibody, and does not induce to generate a T cell reaction aiming at A beta, so that the vaccine has relatively high safety.

In general, disclosed herein are methods for producing a chemoselectively modified biomolecule. The method may include providing a biomolecule, which may include a bioconjugation warhead at a specific site of the biomolecule. Also, the method may include selectively oxidizing the halogen donor compound of the bioconjugation warhead at an electrochemically efficient voltage to generate a halogen radical. Also, the method may include contacting the halogen radical with the bioconjugation warhead at a constant voltage to form an electrophilic warhead. Also, the method may include reacting the electrophilic warhead with a coupling partner comprising a nucleophilic group of the biomolecule to conjugate the electrophilic warhead to the biomolecule.

The application discloses an alcohol side chain labeling method and application. The application reacts a compound containing a Ser residue or a compound containing a Thr residue with fluorosulfonylisocyanate in a solvent to selectively label alcohol side chains in the Ser residue or the Thr residue, and obtain alcohol side chain labeling products. The application can quickly and selectively label the serine and threonine side chains in polypeptides and proteins under mild conditions, and is not interfered by lysine and other hydroxyl-containing structures. The alcohol side chain labeling products can be further reacted, such as sulfur-fluorine exchange substitution reaction with amine to form a conjugate connected by a sulfonamide bond; and can be efficiently removed under the condition of a mild alkaline solution to generate deoxy derivatives with various structures. In summary, the application realizes site-selective editing of the alcohol side chain of a peptide which is difficult to be accurately modified in the prior art, provides a novel and practical technical path for polypeptide drug development and biological conjugate synthesis, and has important synthetic application value.

Described herein are polymeric fluorophores that include a dye, a polymer, and optionally a bioconjugate group. A polymeric fluorophore may have a structure represented by: A-B-C or C-A-B, wherein A is a dye; B is a polymer comprising one or more hydrophobic unit(s) and one or more hydrophilic unit(s); and optionally C, wherein C, when present, comprises a bioconjugate group. Also described herein are compositions comprising the polymeric fluorophores and methods of preparing and using the same.

Provided is a bioconjugation technique, specifically provided is a protein covalent modification technique, i.e., provided is a protein moiety-linker conjugate, which can be used as an intermediate for synthesizing a protein-active molecule conjugate. Further provided are a method for preparing the protein moiety-linker conjugate, and a method for synthesizing a protein-active molecule conjugate by means of using the protein moiety-linker conjugate as an intermediate. The method has a higher conversion rate and fewer by-products.

The present invention in general relates to the field of bioconjugation. More in particular, the invention relates to novel bioconjugation reactants based on an α,β unsaturated γ-hydroxylactam structure, amongst others allowing a higher degree of functionalization compared to classical bioconjugation reactants such as maleimide. The present invention also provides methods of preparing the novel bioconjugation reactants, as well as uses thereof in human and / or veterinary medicine; and conjugation processes.