129Xe biosensors and their use
AssigneeThe Trustees of the University of Pennsylvania
InventorsIvan Dmochowski, Qian Wei, Nicholas Kuzma, P. Aru Hill
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Abstract
This invention relates to enzyme-sensitive biosensors and methods and kits using the same. Specifically, the invention relates to methods, systems and kits for the detection of enzymes using the chemical shift observed in an isotope complexed to the biosensor resulting from a change in the biosensor as the result of the enzyme's activity.
Claims19
A chemical reaction-detection system comprising a biosensor, said biosensor comprises:
- a hyperpolarized noble element complexed with a monopropargyl-cryptophane-A coupled peptide, wherein the peptide is a reactant, specific to said detected chemical reaction and whereby modulation of the reactant induces change in the chemical environment of the noble element resulting in a chemical shift detectable by 29Xe NMR spectroscopy.
A method of detecting and/or analyzing the activity of a matrix metalloproteinase, a caspase, an enzyme, or an integrin in a biological sample of a subject, comprising the steps of:
- contacting the biological sample with a biosensor responsive to said matrix metalloproteinase, caspase, enzyme, or integrin, said biosensor comprising a hyperpolarized noble element complexed with a monopropargyl-cryptophane-A coupled peptide, wherein the peptide is a substrate;
- specific to said detected matrix metalloproteinase, caspase, enzyme, or capable of interacting with the integrin and whereby cleavage of the substrate by the enzyme or internalization of the biosensor coupled to the integrin induces change in the chemical environment of the noble element resulting in a chemical shift detectable by NMR;
- and analyzing the chemical shift in said element, whereby a chemical shift indicates activity of said metalloproteinase or caspase.
A device for screening for the activity of a matrix metalloproteinase, a caspase, an enzyme, or an integrin in a biological sample, comprising a biosensor responsive to said matrix metalloproteinase, caspase, enzyme, or integrin, said biosensor comprising a hyperpolarized noble element complexed with a monopropargyl-cryptophane-A coupled peptide, wherein the peptide is a substrate, specific to said detected matrix metalloproteinase, caspase, enzyme, or capable of interacting with the integrin and whereby cleavage of the substrate by the enzyme or internalization of the biosensor coupled to the integrin induces change in the chemical environment of the noble element resulting in a chemical shift detectable by NMR;
- and instructions for use.
A method of diagnosing a suspected cancer cell in vivo in a subject as malignant or benign, comprising the step of contacting a suspected cell with a composition comprising a fluorescently labeled biosensor wherein said biosensor comprises:
- a hyperpolarized noble element;
- complexed with a monopropargyl-cryptophane-A coupled peptide, wherein the peptide is capable of binding an integrin expressed on the surface of the suspected cancer cell and analyzing the change in fluorescent intensity of the cell before and after administration of the composition, whereby increase in fluorescent intensity, indicates the cell is malignant.
Dependencies are inferred from the claim text.