5584 results about "Cysteine" patented technology

The invention relates to novel binding domain-immunoglobulin fusion proteins that feature a binding domain for a cognate structure such as an antigen, a counterreceptor or the like, a hinge region polypeptide having either zero or one cysteine residue, and immunoglobulin CH2 and CH3 domains, and that are capable of ADCC and/or CDC while occurring predominantly as monomeric polypeptides. The fusion proteins can be recombinantly produced at high expression levels. Also provided are related compositions and methods, including immunotherapeutic applications.

The present invention relates to novel modified proteins having N-terminal free thiols that can be produced by recombinant methods and are ready for further chemical derivatization. In particular, the invention relates to erythropoietin conjugate compounds having altered biochemical, physiochemical and pharmacokinetic properties. More particularly, one embodiment of the invention relates to erythropoietin conjugate compounds of the formula:

(M)_n-X-A-cys-EPO   (I)

where EPO is an erythropoeitin moiety selected from erythropoietin or an erythropoietin variant having at least one amino acid different from the wild-type human EPO, or any pharmaceutical acceptable derivatives thereof having biological properties of causing bone marrow cells to increase production of red blood cells; cys represents the amino acid cysteine and occurs at position −1 relative to the amino acid sequence of the erythropoietin moiety; A indicates the structure of the residual moiety used to chemically attach X to the thiol group of −1Cys; X is a water soluble polymer such as a polyalkylene glycol or other polymer; M is an organic molecule (including peptides and proteins) that increases the circulating half-life of the construct; and N is an integer from 0 to 15.

Antibodies are engineered by replacing one or more amino acids of a parent antibody with non cross-linked, highly reactive cysteine amino acids. Antibody fragments may also be engineered with one or more cysteine amino acids to form cysteine engineered antibody fragments (ThioFab). Methods of design, preparation, screening, and selection of the cysteine engineered antibodies are provided. Cysteine engineered antibodies (Ab) are conjugated with one or more zirconium complex (Z) labels through a linker (L) to form cysteine engineered zirconium-labeled antibody conjugates having Formula I:

Ab-(L-Z)_p  I

where p is 1 to 4. Imaging methods and diagnostic uses for zirconium-radiolabeled, cysteine engineered antibody conjugate compositions are disclosed.

Cysteine engineered antibodies comprising a free cysteine amino acid in the heavy chain or light chain are prepared by mutagenizing a nucleic acid sequence of a parent antibody and replacing one or more amino acid residues by cysteine to encode the cysteine engineered antibody; expressing the cysteine engineered antibody; and isolating the cysteine engineered antibody. Certain highly reactive cysteine engineered antibodies were identified by the PHESELECTOR assay. Isolated cysteine engineered antibodies may be covalently attached to a capture label, a detection label, a drug moiety, or a solid support.

This invention provides methods and devices for spatially separating at least first and second components in a sample which in one exemplary embodiment comprises introducing the first and second components into a first microfluidic channel of a microfluidic device in a carrier fluid comprising a spacer electrolyte solution and stacking the first and second components by isotachophoresis between a leading electrolyte solution and a trailing electrolyte solution, wherein the spacer electrolyte solution comprises ions which have an intermediate mobility in an electric field between the mobility of the ions present in the leading and trailing electrolyte solutions and wherein the spacer electrolyte solution comprises at least one of the following spacer ions MOPS, MES, Nonanoic acid, D-Glucuronic acid, Acetylsalicyclic acid, 4-Ethoxybenzoic acid, Glutaric acid, 3-Phenylpropionic acid, Phenoxyacetic acid, Cysteine, hippuric acid, p-hydroxyphenylacetic acid, isopropylmalonic acid, itaconic acid, citraconic acid, 3,5-dimethylbenzoic acid, 2,3-dimethylbenzoic acid, p-hydroxycinnamic acid, and 5-br-2,4-dihydroxybenzoic acid, and wherein the first component comprises a DNA-antibody conjugate and the second component comprises a complex of the DNA-antibody conjugate and an analyte.

The invention relates to an enzymology measuring method and reagent with circular increment technology, applied to measure the content of homeotypic cysteine in the measured sample. The character is: with a circular increment technology, increases the measurement sensitivity, thus it can carries on automatic measurement to the homeotypic cysteine in the sample liquid like normal enzymology diagnosing agent. The homeotypic cysteine in the sample liquid reacts with the S-adenosine-L-methionine repeatedly and circularly under the effect of homeotypic cysteine methyl kinase and adenosine homeotypic cysteine, generates the adenosine, the speed of the adenosine generation is in direct proportion to the homeotypic cysteine in the sample, through the generation speed, the aim to measure the content of the homeotypic cysteine in sample can be achieved.

Compositions and methods are provided for treating diseases associated with aberrant silencing of gene expression such as cancer by reestablishing the gene expression through inhibition of DNA hypomethylation and histone deacetylase. The method comprises: administering to a patient suffering from the disease a therapeutically effective amount of a DNA methylation inhibitor such as a cysteine analog such as decitabine, in combination with an effective amount of histone deacetylase inhibitor such as hydroxamic acid, cyclic peptide, benzamide, butyrate, and depudecin.

The invention is an enzyme biologic and chemical reaction measure method to mensurate homotype cysteine in a biologic sample. Cysteine can lose its ammonia and be changed into alpha-4-ketone acid, ammonia and sulfureted hydrogen by L-ovi-ammonia acid and Y-dispeling enzyme. Sulfureted hydrogen and fluorescence cpd.DMPD2HCL can create blue product-sub-armour blue whose degree of absorbing light is 670nm, in the situation of Fe3+ and acid. Thus, people can mensurate the chroma of homotype cysteine in a biologic sample by knowing this degree. This method can measure the chroma of homotype cysteine(3-1000 uMs). The invention also involves a reagent box used for implementing the method mentioned above. The box uses liquid double reagents, and needs less quantity of samples(25 microlitre or serum or plasm);In addition, the respond time is short, and the operation is easy. Thus, this method is suitable for a great deal of examinations. The reagent box costs less than other types.

A method for the ligation of expressed proteins which utilizes inteins, for example the RIR1 intein from Methanobacterium thermotrophicum, is provided. Constructs of the Mth RIR1 intein in which either the C-terminal asparagine or N-terminal cysteine of the intein are replaced with alanine enable the facile isolation of a protein with a specified N-terminal, for example, cysteine for use in the fusion of two or more expressed proteins. The method involves the steps of generating a C-terminal thioester-tagged target protein and a second target protein having a specified N-terminal via inteins, such as the modified Mth RIR1 intein, and ligating these proteins. A similar method for producing a cyclic or polymerized protein is provided. Modified inteins engineered to cleave at their C-terminus or N-terminus, respectively, and DNA and plasmids encoding these modified inteins are also provided.

The present invention provides water-soluble, polymer derivatives having a thiol-selective terminus suitable for selective coupling to thiol groups, such as those contained in the cysteine residues of proteins.

L-Cysteine is produced by culturing a microorganism having an ability to produce L-cysteine and modified so that expression of emrAB, emrKY, yojIH, acrEF, bcr, or cusA gene should be enhanced in a medium to produce and accumulate L-cysteine in the medium and collecting the L-cysteine from the medium. Genes coding for novel L-cysteine-excreting proteins are identified, and utilized for breeding of L-cysteine-producing microorganism to provide a novel method of producing L-cysteine.

The present invention sets forth a new chemical genetic approach for engineering kinase enzymes with a cysteine gatekeeper residue as well as for developing electrophilic inhibitors thereto. The present invention also provides a Src proto-oncogenic tyrosine kinase with a cysteine gatekeeper that recapitulates wild type activity and can be irreversibly inhibited both in vitro and in cells. The present invention also provides methods and compositions for modulating kinases and for treating kinase-associated diseases.

The invention provides a nutritional supplement which includes micronutrients to facilitate reduction of cholesterol, and/or reduction of homocystein and/or reduction of low-density lipoprotein-cholesterol (LDL-C) oxidation in humans. In one embodiment the supplement is a multi-vitamin, a mineral supplement which includes at least one component known to reduce cholesterol. The invention further provides a method for tableting one fourth to one half of the daily effective dosage of a phytosterol containing nutritional supplement in a practical sized tablet and a method for reducing blood cholesterol in humans.

The present invention relates to nucleic acid sequences and amino acid sequences which influence bone deposition, the Wnt pathway, ocular development, tooth development, and may bind to LRP. The nucleic acid sequence and polypeptides include Wise and Sost as well as a family of molecules which express a cysteine knot polypeptide. Additionally, the present invention relates to various molecular tools derived from the nucleic acids and polypeptides including vectors, transfected host cells, monochronal antibodies, Fab fragments, and methods for impacting the pathways.

Cysteine engineered antibodies useful for the site-specific conjugation to a variety of agents are provided. Methods for the design, preparation, screening, selection and use of such antibodies are also provided.

The present invention provides compositions and methods of use of anti-IGF-1R antibodies or antibody fragments. Preferably the antibodies bind to IGF-1R but not IR; are not agonists for IGF-1R; do not block binding of IGF-1 or IGF-2 to isolated IGF-1R, but effectively neutralize activation of IGF-1R by IGF-1 in intact cells; and block binding of an R1 antibody to IGF-1R. The antibodies may be murine, chimeric, humanized or human R1 antibodies comprising the heavy chain CDR sequences DYYMY (SEQ ID NO:1), YITNYGGSTYYPDTVKG (SEQ ID NO:2) and QSNYDYDGWFAY (SEQ ID NO:3) and the light chain CDR sequences KASQEVGTAVA (SEQ ID NO:4), WASTRHT (SEQ ID NO:5) and QQYSNYPLT (SEQ ID NO:6). Preferably the antibodies bind to an epitope of IGF-1R comprising the first half of the cysteine-rich domain of IGF-1R (residues 151-222). The anti-IGF-1R antibodies may be used for diagnosis or therapy of various diseases such as cancer.

Elevated levels of homocysteine have been implicated as an important risk factor for cardiovascular and other diseases. A composition for decreasing levels of plasma homocysteine and a method for administering the composition are provided, the composition containing dextromethorphan (DM), folic acid and vitamins B6 and B12. The composition provides a synergistic therapeutic effect so that lower amounts of the above ingredients may be employed to minimize any undesirable side effects caused by the use of high levels of a component such as DM. Preferred compositions for cardiovascular diseases further include lecithin, vitamin E, betacarotene, procyanidins/flavonoids, trimethylglycine, garlic oil and minerals. Other compositions for treating glaucoma include bilberry, bioflavonoids and beta-carotene and for treating tardive dyskinesia include an antioxidant such a grape seed extract and pine bark extract, lecithin and oligomeric proanthocyanidins. The compositions may be administered using any suitable means such as orally or intravenous.

The invention discloses a molybdenum disulfide (MoS2) nano-sheet film material and its preparation methods. The film material is characterized in that MoS2 nano-sheets vertically and sequentially grow on a conductive substrate, and the diameters and the thicknesses of the MoS2 nano-sheets are 0.05-2mum and 2-30nm respectively. There are two preparation methods of the film material. One preparation method comprises the following steps: a substrate which can be a copper sheet, a silver sheet, a titanium sheet, a tungsten sheet, a molybdenum sheet or carbon is placed in a solution comprising a molybdate and sulfur-containing compounds (comprising thiourea, thioacetamide and L-cysteine); and the sulfur-containing compounds undergo a hydrothermal reaction to grow the compactly-grown and uniformly-sequential MoS2 nano-sheet films on the substrate. Another method comprises the following steps: the molybdenum sheet is directly placed in a solution of the sulfur-containing compounds (comprising thiourea, thioacetamide and L-cysteine); and the sulfur-containing compounds undergo a sulfuration reaction under a hydrothermal condition to form the compact and uniform MoS2 nano-sheet ordered films. The film has a low hydrogen evolution overpotential (-30mv), a small Tafel slope (52mV/dec) and a high electrochemical stability, and is a hydrogen evolution electrode material extremely having an application prospect.

The present invention is directed to stable protein derivatives, e.g., antibodies, antibody fragments or peptides, with at least one free thiol group coupled to N-acetyl-L-cysteine, N-ethyl-maleimide, or cysteine and the methods of making such derivatives. In addition, stable liquid pharmaceutical formulations comprising such proteins or their derivatives and stable lyophilized pharmaceutical formulations comprising such proteins are provided. The present invention is also directed to a method of making a stable Fab′ fragment of an antibody and a method of controlling vascularization in injured or cancerous tissue comprising applying to the injured tissue one or more doses of the pharmaceutical formulations.