43 results about "Bioconjugation" patented technology

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.

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.

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.

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 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.

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.

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.

The present disclosure relates to a quinolinone derivative compound selectively binding to cysteine, an amino acid- or peptide-conjugate thereof, and an antibody-drug conjugate comprising same. Since a conjugate with high chemoselectivity and high yield is formed through a radical pathway induced by visible light, the present disclosure can be applied in various ways to bioconjugation.

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 compounds of general structure (1): Q-(L1)n-(L2)o-(L3)p-(L4)q-D (1), wherein Q is a click probe; D is a cytotoxin containing an enediyne moiety; L1, L2, L3 and L4 are each individually linkers that together link Q to D; n, o, p and q are each individually 0 or 1, provided that n+o+p+q=1, 2, 3 or 4, wherein D comprises a functional moiety (21):wherein R12=C1-3-alkyl, the wavy line indicates the connection to the remainder of the cytotoxin, and wherein D is conjugated to (L4)q by replacing the amine H atom, and to conjugates obtainable by reacting the compound according to the invention with a protein comprising a click probe F capable of reacting with click probe Q in a click reaction. The invention further relates to a bioconjugate according to general structure (2): Pr-[(L6)-Z-(L1)n-(L2)o-(L3)p-(L4)q-D]xx (2), wherein Z is a connecting group that is formed in a click reaction, L6 is a linker that links Z to Pr and Pr is a (glyco)protein.

The present invention relates generally to the field of bioconjugation. More particularly, the present invention relates to trivalent phosphonates and their use as reducing disulfide heavy bridging agents. Accordingly, the present invention relates to compounds selected from the group consisting of compounds of formula (la) and (lb), conjugates obtained by linking these compounds to another moiety, methods of modifying disulfide containing compounds using compounds selected from the group consisting of compounds of formula (la) and (lb), and compounds obtained by such methods.

The invention relates to IL-17A binding peptides, inhibitors of the interaction of IL-17A with the receptor IL-17RA, and to bioconjugates, dimers, pharmaceutical compositions and medical use thereof.

The present disclosure relates to site-specific modification of antibodies at their Fc glycan sites, and subsequent conjugation to drugs and other entities, to produce structurally explicitly defined antibody conjugates. The method is based on the discovery that N-azidoacetylglucosamine GlcNAz-derived sugar oxazolines can be used as substrates for endoglycosidases such as Endo S2 and Endo S for enzymatic Fc glycan remodeling to site-specifically introduce the azide tag in the antibody in a single step, such as in a single step, for example, in the antibody. A click reaction is then performed to form a site-specific antibody-drug conjugate and an antibody-ligand conjugate.

Described in several example embodiments herein are engineered split intein polypeptides and systems thereof. Also described in several example embodiments, herein are methods of using the engineered split intein polypeptides and systems thereof, such as to catalyze a bioconjugation reaction.

Described herein is a visible light enabled photocatalytic oxidative protein bioconjugation reaction directed towards site-specifically incorporating non-canonical amino acids (ncAA).

Anionically functionalized polypeptides, methods of making same, and uses thereof. Anionically functionalized polypeptides comprise one or more anionic group(s), where each anionic group is covalently bound to an anionically functionalized polypeptide sidechain or N-terminus, and one or more cleavable group(s). Anionically functionalized polypeptides can be made by reaction of a bioconjugation reagent comprising one or more anionic group(s) with a polypeptide, which may be a modified polypeptide. Anionically functionalized polypeptides can be used, in various examples, to intracellularly deliver a polypeptide, in cell transfection methods, or in treatment methods.

Described herein is a dual-functional tetrazine–allyl reagent that enables site-selective disulfide modification in peptides and proteins, serving both as a Michael acceptor for bis-thiols and as a reactive handle for Inverse Electron-Demand Diels–Alder (IEDDA) click chemistry to introduce functional payloads.

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 involves the conjugation of tubulysin derivatives (analogs) to cell-binding molecules via branched (side chain) linkers, with the resulting conjugates having better pharmacokinetic properties and thus enabling more precise targeting and killing of diseased cells. The present invention also relates to methods for synthesizing the conjugates of tubulysin analogs to cell-binding agents and the molecules involved therein, as well as targeted treatment of cancer, infectious diseases, and autoimmune diseases using the conjugates. Conjugates of tubulysin with long branched linkers extend half-life during targeted delivery and minimize exposure to non-target cells, tissues, or organs in the blood circulation, thereby reducing off-target toxicity.

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.

The invention discloses a biological coupling method for polypeptide / protein main chain modification and synchronous fluorescence labeling, a conjugated receptor structure and application, and belongs to the technical field of polypeptide / protein coupling methods, chemically selective thiol coupling is achieved through conjugated receptors (CAs) derived from divinyl sulfide, the reaction process comprises amide activation and five-membered ring formation, and the conjugated receptors (CAs) are subjected to fluorescence labeling. Fluorescence labeling can be synchronously achieved, the fluorescence opening effect can be optically monitored in real time, and a built-in sensing mechanism is provided for dynamic reaction tracking. According to the invention, the technical problem that the polypeptide / protein main chain is difficult to modify due to factors such as poor stability, low biocompatibility, need of introducing an exogenous sequence and the like in the existing modification method is effectively solved, and a novel orthogonal technical platform is provided for protein engineering, biological conjugate development, drug design and biomolecular sensing; the method is suitable for the biomedical fields of biomarkers, fluorescence imaging, polypeptide / protein activity regulation and control and the like.

Methods are provided for producing bioconjugates of O-antigen polysaccharides covalently linked to a carrier protein using recombinant host cells. The recombinant host cells used in the methods described herein encode a particular oligosaccharyl transferase enzyme depending on the O-antigen polysaccharide bioconjugate intended for production. The oligosaccharyl transferase enzymes can be Pg1B oligosaccharyl transferase or variants thereof. Also provided are compositions containing the bioconjugates, and methods of using the bioconjugates and compositions described herein for vaccinating an individual against extra-enteric pathogenic E. coli (ExPEC).

The invention relates to chemical, electrochemical and non-covalently bioconjugation (functionalization) of proteins with catalytic properties. A functionalization method is disclosed using all organic solvents except dimethylformamide (DMF), and dimethyl sulfoxide (DMSO), and utilizing organic synthesis and non-covalent insertion methods. Furthermore, the invention encompasses the preparation of bioelectrodes designed for the detection of substances, including but not limited to glucose, lactose, galactose (as carbohydrates), dopamine, adrenaline (epinephrine), noradrenaline (norepinephrine), and serotonin (as neurotransmitters), L-glutamate, D- or L-amino acids, hydrogen peroxide, nicotine, cholesterol, ethanol, oxalate, lactate, and pyruvate in food products, as well as in human body fluids serving as real samples. Additionally, this invention extends to the utilization of bioelectrodes for monitoring chemical processes, including features and the chemical environment of neuron interfaces within the brain. The invention encompasses an electrochemical inhibitor testing system utilizing the aforementioned bioelectrodes, and the functionalized proteins as single-molecular protein-based memristors.