Chelating Agents for Stable Lanthanide Labeling
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Solution Overview
Problem
Current methods for labeling biomolecules with lanthanide chelates are laborious and inefficient, especially for large biomolecules and multiparameter assays, due to the need for selective and effective conjugation reactions that are difficult to achieve in solution phase, leading to challenges in sensitivity and stability required for applications like time-resolved fluorometric assays, MRI, and PET.
Innovation Solution
Development of chelating agents with a chromophoric moiety comprising trialkoxyphenylpyridyl groups and carboxylic acid or phosphonic acid groups, which form stable metal chelates with lanthanide ions, enabling strong fluorescence and suitable for use in time-resolved fluorescence spectroscopy, MRI, and PET, and can be conjugated to biomolecules or solid supports for improved labeling efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If solution phase labeling is used for large biomolecules, then labeling flexibility is improved, but labeling selectivity and effectiveness deteriorate
Solution Approach 1:
The patent introduces a solid support as an intermediary carrier that bears the chelating agent. This solid support mediates the labeling reaction by providing a fixed platform for the chelating agent to interact with biomolecules, thereby improving labeling selectivity while maintaining flexibility through various solid support formats and reaction conditions.
Solution Approach 2:
The patent modifies the physical state and chemical environment parameters of the labeling system by transitioning from homogeneous solution phase to heterogeneous solid support phase. This parameter change enables better control over labeling selectivity through controlled interaction between the immobilized chelating agent and biomolecules.
2Productivity
If excess activated label is used for conjugation, then labeling effectiveness is improved, but purification complexity increases
Solution Approach 1:
The solid support acts as an intermediary that simplifies the purification process. By immobilizing the chelating agent on the solid support, unreacted excess label naturally remains bound to the support while the labeled biomolecule is released into solution, enabling simple separation through filtration or centrifugation without complex purification procedures.
Solution Approach 2:
The patent extracts the unreacted excess label from the reaction mixture by keeping it bound to the solid support phase, while the desired labeled product is extracted into the solution phase. This phase separation effectively removes excess reagent without requiring additional purification steps.
3Measurement precision
If site-specific labeling is required, then assay precision is improved, but reaction selectivity becomes more difficult to achieve
Solution Approach 1:
The solid support serves as an intermediary platform that enables site-specific labeling by controlling the orientation and accessibility of the chelating agent. This controlled presentation on the solid support facilitates selective reaction with specific functional groups on the biomolecule, achieving both high reaction selectivity and assay precision.
4Illumination intensity
If multiple label molecules are attached, then signal intensity is improved, but conjugate characterization becomes extremely difficult
Solution Approach 1:
The solid support acts as an intermediary that simplifies the characterization of multiply-labeled conjugates. By controlling the labeling reaction on the solid support and using techniques like mass spectrometry or HPLC on the released conjugate, the patent enables characterization of multiple label attachments without the extreme difficulty associated with solution phase random labeling.
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
The new chelating agents provide strong, stable fluorescence and can be used for multiparameter bioaffinity assays and high-throughput screening, offering improved sensitivity and stability for in vivo applications, reducing the need for laborious purification procedures and enhancing the labeling of biomolecules in solution and on solid phases.
Implementation Method 1
Because of their unique luminescence properties lanthanide(III) chelates are often used as non-radioactive markers
Implementation Method 2
the chromophoric moiety comprising two or more aromatic units, wherein at least one of the aromatic units is a trialkoxyphenylpyridyl group
Implementation Method 3
a chelating part comprising at least two carboxylic acid or phosphonic acid groups, or esters or salts of said acids
Data Source
AI summary
This invention relates to a group of novel chelating agents, novel chelates, biomolecules labeled with said chelates or chelating agents as well as solid supports conjugated with said chelates, chelating agents or labeled biomolecules. Especially the invention relates to novel chelating agents useful in solid phase synthesis of oligonucleotides or oligopeptides and the oligonucleotides and oligopeptides so obtained.