Reporter Molecules with Multiple Handle Groups for Click Chemistry

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Solution Overview

Problem

Current methods for producing reporter molecules can only incorporate a single type of labelling group site-specifically, limiting versatility in modification and detection capabilities.

Innovation Solution

Incorporating at least two different handle groups into reporter molecules during synthesis, allowing for selective coupling of distinct functional groups via reactions like the Click reaction, enabling the site-specific incorporation of multiple labelling groups.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If a single type of labelling group is incorporated into the reporter molecule, then the synthesis is simple and straightforward, but the versatility in modification and detection capabilities is limited

Engineering Contradiction:
Improveversatility in modificationVSAvoidcomplexity of incorporating multiple handle groups
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The reporter molecule is divided into multiple segments, each containing a specific handle group (alkyne, azide, aldehyde, hydrazine, or hydroxylamino). This segmentation allows independent functionalization of different parts of the molecule with different labelling groups, achieving versatility while maintaining manageable synthesis complexity through modular design

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention creates a universal platform where the reporter molecule can accommodate multiple types of handle groups that are compatible with Click chemistry and related reactions. This multi-functional design enables the same reporter molecule to be adapted for various detection applications by selectively coupling different labelling groups to different handle groups

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If multiple handle groups are incorporated into the reporter molecule for site-specific labelling, then the detection versatility is enhanced, but the synthesis process becomes more complex

Engineering Contradiction:
Improvedetection capabilitiesVSAvoidease of incorporating multiple handle groups
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The handle groups are pre-installed into the reporter molecule during the synthesis phase, before the actual labelling process. This preliminary action ensures that the handle groups are correctly positioned and protected during synthesis, simplifying the subsequent labelling steps and making the overall process more manageable despite the increased complexity of incorporating multiple handle groups

Inventive Principle:
Principle #10Preliminary action

3Productivity

If reactive handle groups are used for selective coupling, then the labelling efficiency is high, but side reactions may occur

Engineering Contradiction:
Improvelabelling efficiencyVSAvoidside reactions
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The invention utilizes the high reactivity of handle groups towards Click chemistry reactions to achieve efficient labelling. The specific chemical properties of each handle group (alkyne, azide, aldehyde, hydrazine, hydroxylamino) are leveraged to enable selective and efficient coupling with corresponding labelling groups, converting what could be potential side reactions into beneficial selective reactivity through orthogonal chemistry

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The handle groups act as intermediaries between the reporter molecule and the labelling groups. These intermediaries provide controlled reactivity, enabling selective coupling reactions while minimizing unwanted side reactions through the specific chemical properties of each handle group type

Inventive Principle:
Principle #24Intermediary (Mediator)

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

Enables the efficient production of reporter molecules with multiple functional groups for sensitive detection of analytes, such as nucleic acids, without significant side reactions, enhancing detection sensitivity and versatility in applications like genetic analysis and diagnostics.

Implementation Method 1

The terminal alkyne is a reactive site for the Click reaction, which is a copper-catalysed Huisgen dipolar cycloaddition between azides and alkynes

Methodology Applied
Scientific EffectClick reaction: Chemical Bonding

Data Source

PatentUS8193335B2Click chemistry for the production of reporter molecules
Publication Date: 2012.06.05 BASECLICK
  • US8193335B2 patent drawing
  • US8193335B2 patent drawing
  • US8193335B2 patent drawing

AI summary

The present invention relates to methods for producing reporter molecules suitable for the detection of analytes, e.g. nucleic acids. Further, the present invention relates to methods and regions for detecting analytes.