Cyclooctyne Quinone Radiolabeling for Stable Biomolecules
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Solution Overview
Problem
Existing radiolabeling methods for biomolecules, particularly using radioactive iodine, face challenges such as low reaction rates, instability in living cells, and the need for organic solvents, which limits their application in medical diagnosis and treatment.
Innovation Solution
A method involving a cyclooctyne compound bound to a biomolecule, fluorescent dye, or nanoparticle, reacting with a quinone compound labeled with a radioisotope at room temperature without the use of organic solvents, enabling a fast and stable radiolabeling process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If electrophilic aromatic substitution reaction is used for labeling radioactive iodine, then labeling efficiency is improved, but stability in animal bodies deteriorates
Solution Approach 1:
The patent introduces a prosthetic group as an intermediary between the biomolecule and radioactive iodine. The prosthetic group contains a phenolic hydroxyl group that reacts with radioactive iodine to form a stable ether bond, while the other end connects to the biomolecule. This intermediary structure enables efficient labeling while maintaining stability in animal bodies, resolving the contradiction between labeling efficiency and in vivo stability.
2Stability of the object's composition
If indirect labeling method with prosthetic groups is used, then stability in animal bodies is improved, but reaction rate deteriorates
Solution Approach 1:
The patent modifies the parameters of the prosthetic group structure, specifically using a phenolic hydroxyl group with appropriate pKa value and steric configuration. These structural parameter changes enable the prosthetic group to react rapidly with radioactive iodine while maintaining stability in animal bodies, thus improving reaction rate without sacrificing stability.
3Ease of manufacture
If conventional radiolabeling methods are used, then labeling can be achieved, but organic solvents are required which limits application in living cells
Solution Approach 1:
The patent extracts and eliminates the requirement for organic solvents from the radiolabeling process. By designing a prosthetic group with phenolic hydroxyl group that can react with radioactive iodine in aqueous physiological conditions, the method removes the need for toxic organic solvents like DMSO or acetonitrile, thereby enabling application in living cells and animals while maintaining labeling capability.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach results in a high reaction rate and radiochemical yield, providing stable radiolabeling with reduced thyroid gland accumulation of iodine-125, suitable for medical diagnostic and therapeutic compositions.
Implementation Method 1
reacting the cyclooctyne compound with a quinone compound represented by the following formula (II) and labeled with the radioisotope
Data Source
AI summary
The present disclosure relates to a method for labeling a biomolecule, a fluorescent dye, or a nanoparticle compound with a radioisotope, comprising: (a) providing a cyclooctyne compound represented by the following formula (I) comprising the biomolecule, the fluorescent dye, or the nanoparticle compound which is bound to a cyclooctyne moiety of the cyclooctyne compound; and (b) reacting the cyclooctyne compound of formula (I) with a quinone compound represented by the following formula (II) to give a biomolecule, a fluorescent dye, or a nanoparticle compound labeled with the radioisotope:in formula (I), (Z is the biomolecule, the fluorescent dye, or the nanoparticle compound)in formula (II), (b is 0 or an integer from 1 to 10; L is CH2, —COO—, or —CONH—; M is the radioisotope).