Polymeric Tandem Dyes with Linker Groups for FRET
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Solution Overview
Problem
Existing fluorescent and colored dyes used in resonance energy transfer techniques, such as FRET, suffer from limitations related to orientation and positioning of chromophores, energy transfer masking by free fluorophores, and pH sensitivity, leading to a need for water-soluble dyes with increased molar brightness and FRET emission signal.
Innovation Solution
Development of dimeric and polymeric chromophore compounds with spacing groups that are covalently linked by a linker, optimizing intramolecular FRET interactions and enhancing molar brightness and FRET emission signal.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Illumination intensity
If monomeric dyes are used, then the dye structure is simple, but the molar brightness and FRET emission signal are insufficient
Solution Approach 1:
The patent combines multiple chromophores into dimeric and polymeric structures through covalent linkers, merging individual dye units to achieve enhanced molar brightness and FRET emission signals that exceed the sum of monomeric components
2Illumination intensity
If chromophores are positioned close together to enhance FRET, then FRET emission signal increases, but energy transfer masking by free fluorophores occurs
Solution Approach 1:
The patent segments the dye structure into distinct chromophore units connected by linkers of specific lengths, allowing optimization of the distance between donor and acceptor chromophores to enhance FRET while minimizing masking effects from free fluorophores
Solution Approach 2:
The patent introduces linker molecules as intermediaries between chromophores, with specific linker lengths (e.g., L1-L6) that mediate the distance and orientation between donor and acceptor, optimizing FRET efficiency while preventing energy transfer masking
3Adaptability or versatility
If dyes are designed for aqueous environments, then compatibility with biological systems improves, but pH sensitivity increases
Solution Approach 1:
The patent creates composite dye structures combining multiple chromophores with different pH stability characteristics, where the polymeric framework provides overall structural stability while individual chromophore units contribute to aqueous solubility and biological compatibility
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 described dyes are significantly brighter than monomeric counterparts, enabling efficient FRET processes and allowing for visual detection of analyte molecules with improved spatial and temporal resolution.
Implementation Method 1
Förster resonance energy transfer ('FRET'-sometimes also used interchangeably with fluorescence resonance energy transfer) techniques produce information that reliably measures change biomolecular distances and interactions
Implementation Method 2
The water soluble, fluorescent or colored dyes of embodiments of the invention are intensely colored, enable FRET processes (e.g., absorbance, emission, Stokes shifts) and/or fluorescent
Data Source
AI summary
Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I), or a stereoisomer, tautomer or salt thereof, wherein R1, R2, R3, R4, R5, L1, L2, L3, L4, M1, M2, m and n are as defined herein. Methods associated with preparation and use of such compounds is also provided.


