124results about "Isotope introduction to peptides/proteins" patented technology

Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

Disclosed are compositions and methods for sensitive detection of one or multiple analytes. In general, the methods involve the use of special label components, referred to as multidimension signals. In the disclosed methods, analysis of multidimension signals can result in one or more predetermined patterns that serve to indicate whether a further level of analysis can or should be performed and / or which portion(s) of the analyzed material can or should be analyzed in a further level of analysis. In some forms, isobaric and non-isobaric elements can be used together in the same assay or assay system. Isobaric and non-isobaric multidimension signals used together can generate one or more predetermined patterns during analysis. The pattern generated in this first level of analysis indicates whether the second level of analysis should be performed. The second level of analysis can involve distinguishing the isobaric multidimension signals.

Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic kit facilitating relative quantification and providing tangible evidence for the existence of specific functional groups. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules, such as biological samples. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. Advantageously, the labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC / MS) applications. Labeled primary and secondary amine and carboxylic acid end-products also generated higher signals concerning mass-spectra than pre-cursor molecules and improved sensitivity. Improved accuracy concerning relative quantification was achieved by mixing heavy and light labeled Arabidopsis extracts in different ratios. Labeling strategy was further employed to ascertain differences in the amounts of amine-containing metabolites for two strains of Arabidopsis seeds.

Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

Methods for introducing fluorine atom onto a polypeptide are provided. Also provided are linkers, bioconjugates, and bifunctional compound agents made using the methods, linkers, and bioconjugates. The methods comprise: (i) providing a linker comprising a thiol-reactive terminus and an aldehyde-reactive terminus; (ii) reacting the thiol-reactive terminus of the linker with a polypeptide comprising at least one thiol group or a reactive derivative thereof; and (iii) subsequently reacting the aldehyde-reactive terminus of the linker with a fluorine-substituted aldehyde.

F-18 radiolabeled peptides are prepared by reacting a peptide comprising a hydroxylamine, a thiosemicarbazide, a hydrazine or a free amine group with 4-[18F]Fluorobenzaldehyde. Specific, non-limiting examples of F-18 radiolabeled peptides are described herein. The labeled peptides are useful, for example, in clinical positron emission tomography.

Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic kit facilitating relative quantification and providing tangible evidence for the existence of specific functional groups. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules, such as biological samples. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. Advantageously, the labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC / MS) applications. Labeled primary and secondary amine and carboxylic acid end-products also generated higher signals concerning mass-spectra than pre-cursor molecules and improved sensitivity. Improved accuracy concerning relative quantification was achieved by mixing heavy and light labeled Arabidopsis extracts in different ratios. Labeling strategy was further employed to ascertain differences in the amounts of amine-containing metabolites for two strains of Arabidopsis seeds.

The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites / proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor / scaffold proteins, adhesion / extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding / repair / replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G / regulator proteins, inhibitor proteins, motor / contractile proteins, phosphatase, protease, Ser / Thr protein kinases, protein kinase (Tyr)s, receptor / channel / cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

Provided herein are antibodies and methods of using the antibodies to treat and diagnose neurite degenerative diseases and disorders.

A process for determining the sequence of nucleic acids of interest employs nucleotides or nucleotide analogs that have been made detectable by non-radioactive modifying or labeling. Such nucleotides or nucleotide analogs are modified on the sugar moieties, the phosphate moieties or the base moieties, including base analogs. Modified nucleotide analogs can be attached to or coupled to or incorporated into DNA or RNA. The modified or labeled nucleotides or nucleotide analogs are also useful in processes for detecting the presence of nucleic acids of interest and for characterizing chromosomal sequences. Detection processes using the modified or labeled nucleotides or nucleotide analogs extend to the use of a gel for separating or resolving hybrids formed between non-radioactively labeled oligonucleotides or polynucleotides and such nucleic acids of interest.

Certain embodiments of the present invention relate to a system and a method for producing a radiopharmaceutical, wherein the system is formed from and / or provides a microfluidic flow system. In certain embodiments, the system comprises a radioisotope isolation module, a radiopharmaceutical production module, a purification module and a quality control module.

The present invention relates to the use of Heat Shock Proteins and fragments thereof as targeting ligand. The Heat Shock Protein may be labeled with imaging agents that are capable of binding lectin-like oxidized low-density lipoprotein (LOX-1) or may be attached to a therapeutic agent. The sequences are useful for the diagnosis and monitoring of diseases as well as means for internalizing signaling moieties and therapeutics.

The invention relates to conjugates of formula (V) or (VI): wherein X is —CO—NH—, —NH—, —O—, —NHCONH—, or —NHCSNH—; their use as radiopharmaceuticals, processes for their preparation, and synthetic intermediates used in such processes.