123results about "Isotope introduction to peptides/proteins" patented technology

Thiol-containing peptides can be radiolabeled with fluorine-18 (F-18) by reacting a peptide comprising a free thiol group with an F-18-bound labelling reagent which also has a group that is reactive with thiols. The resulting F-18-labeled peptides may be targeted to a tissue of interest using bispecific antibodies or bispecific antibody fragments having one arm specific for the F-18-labeled peptide or a low molecular weight hapten conjugated to the F-18-labeled peptide, and another arm specific to the targeted tissue. The targeted tissue is subsequently visualized by clinical positron emission tomography.

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]Fluorobenzaledyde. Specific, non-limiting examples of F-18 radiolabeled peptides are described herein. The labeled peptides are useful, for example, in clinical positron emission tomography.

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.

The invention relates to a method and a kit for preparing a radiopharmaceutical, the method comprising the steps:

• • elution of a ⁶⁸Ge/⁶⁸Ga-Generator using hydrochloric acid as an eluent for obtaining a generator eluate comprising ⁶⁸Gallium,
  • feeding the generator eluate through a cation exchange cartridge, which collects the ⁶⁸Gallium,
  • separating the used eluent,
  • eluting the ⁶⁸Gallium from the cation exchange cartridge using a solution comprising sodium chloride and hydrochloric acid and feeding the resulting eluate into an aqueous precursor mixture comprising at least a labelling precursor thereby forming a reaction solution.

The invention discloses 168 novel phosphorylation sites identified in signal transduction proteins and pathways downstream of, and including, EGFR kinase, 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: Actin Binding proteins, Adaptor/Scaffold proteins, Calcium-Binding Proteins, Cell Cycle Regulation proteins, Cytoskeletal proteins, DNA Binding and Replication Proteins, GTPase Activating proteins, Guanine Nucleotide Exchange Factor proteins, Lipid Kinases, Receptor Tyrosine Kinases, Receptor Tyrosine Kinase ligands, Protein Kinases, Receptor and Protein Phosphatases, Transcription Factor proteins, Tumor Suppressor proteins, and Vesicle proteins.

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.

The present invention relates to methods and reagents for [¹⁸F]-fluorination, particularly of peptides. The resultant ¹⁸F-labelled compounds are useful as radiopharmaceuticals, specifically for use in Positron Emission Tomography (PET). Thus, a compound of formula ¹⁸F-(Linker)-SH, such as a compound of formula (IV), (V), or (VI):

¹⁸F—(CH₂CH₂O)_n—(CH₂)_m—SH   (IV)

¹⁸F—(CH₂)_p—SH   (V)

may be reacted with an activated peptide as a means for ¹⁸F-labelling.

The present application discloses compositions and methods of synthesis and use involving click chemistry reactions for in vivo or in vitro formation of therapeutic and/or diagnostic complexes. Preferably, the diagnostic complex is of use for 18F imaging, while the therapeutic complex is of use for targeted delivery of chemotherapeutic drugs or toxins. More preferably, a chelating moiety or targetable construct may be conjugated to a targeting molecule, such as an antibody or antibody fragment, using a click chemistry reaction involving cyclooctyne, nitrone or azide reactive moieties. In most preferred embodiments, the click chemistry reaction occurs in vivo. In vivo click chemistry is not limited to 18F labeling but can be used for delivering a variety of therapeutic and/or diagnostic agents.

Embodiments of the present invention relates to compounds labeled with imaging agents that also are capable of binding lectin-like oxidized low-density lipoprotein (LOX-1). The labeled compounds are useful for the diagnosis and monitoring of diseases in which inflammation plays a role, such as various cardiovascular diseases including but not limited to atherosclerosis, vulnerable plaque, and coronary artery disease, as well as rheumatoid arthritis.

This invention provides an NMR method for obtaining both entropic and enthalpic data on proteins and protein/ligand complexes which can be used to obtain accurate structural and dynamic data of proteins and protein complexes having a wide range of molecular weights. An embodiment of the invention provides proteins which contain at least one bond vector whose dynamics are to be measured and which is surrounded by NMR inactive nuclei, and amino acids for synthesis of the proteins via chemical means or biological expression. The NMR methods using specifically labeled proteins for analysis result in maximization of the sensitivity and resolution of the NMR experiments, and minimization of the loss of signal due to diffusion.

Novel radiotracer(s) for Positron Emission Tomography (PET) imaging are described. Novel radiotracer(s) for Positron Emission Tomography (PET) imaging of neuorendocrine tumors are described. Specifically the present invention describes novel [18F]Fluoroethyltriazol-[Tyr3]Octreotate analogs; in particular those that target somatostatin receptors found on the cell surface of gastroenteropancreatic neuorendocrine tumors. The present invention also describes intermediate(s), precursor(s), pharmaceutical composition(s), methods of making, and methods of use of the novel radiotracer(s).

The invention discloses 322 novel acetylation sites identified in various cancers, peptides (including AQUA peptides) comprising a acetylation site of the invention, antibodies specifically bind to a novel acetylation site of the invention, and diagnostic and therapeutic uses of the above.

The invention relates to a complex of a bifunctional connecting agent realizing core coordination with carbonyl metal and a preparation method thereof, and belongs to the technical field of radiopharmaceutical chemistry. The bifunctional connecting agent is N,N'-bi[2-hydroxyl-5-( propyloic) benzyl] ethylenediamine-N,N'-oxalic acid, and has a structure shown in the description, wherein at least onein R1 and R2 is a targeted small molecule or polypeptide or protein big molecule; the metal is Tc or Re. The carbonyl Tc/Re core marked HBED-CC complex is successfully obtained for the first time, different nuclide (68Ga, 99mTc/Re) marks of the same marking precursors can be realized; by aiming at the mutual supplementation of two development modes (PET/SPECT) in the same target point, the 188/186Re complex can be used for radioactive therapy medicine study. A novel idea is provided for the development of a Tc-99m single photon radioactive tracer agents and Re-188/186 radioactive treatment medicine; meanwhile, the application range of the HBED-CC derivatives as radiopharmaceutical marker precursors is also expanded.

A process for the preparation of complexes containing ⁶⁸Ga wherein a buffer formic acid/formate in the presence of compounds capable to sequester metal cations is used in the complexion reaction.

The present disclosure relates to the synthesis of radionuclide complex solutions, in particular for their use in the commercial production of radioactive drug substances, for diagnostic and/or therapeutic purposes. In particular, the synthesis method comprises the following steps in the following order:

• • a. providing a radionuclide precursor solution into a first vial,
  • b. transferring the radionuclide precursor solution into a reactor,
  • c. providing a reaction buffer solution into said first vial containing residual radionuclide precursor solution,
  • d. transferring the buffer reaction solution and residual radionuclide precursor solution from said first vial into the reactor,
  • e. transferring a peptide solution comprising the somatostatin receptor binding peptide linked to a chelating agent, into the reactor,
  • f. reacting the somatostatin receptor binding peptide linked to a chelating agent with said radionuclide in the reactor to obtain the radionuclide complex,
  • g. recovering said radionuclide complex.

The invention relates to conjugates of formula (V) or (VI), their use as radiopharmaceuticals, processes for their preparation, and synthetic intermediates used in such processes.