Labeled Polypeptide PEG Linker Binding Efficiency

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Solution Overview

Problem

Existing methods for binding functional substances to glutamine residues in polypeptides using bifunctional linkers do not achieve high efficiency.

Innovation Solution

A labeled polypeptide is created using a polyethylene glycol (PEG) chain with a thiol group and an amino group as a bifunctional linker, where the PEG chain has a molecular weight of 1100 or larger, allowing efficient binding to the glutamine residue through a TG-catalyzed reaction, followed by attachment of a maleimide group-containing label.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If a bifunctional linker is used to bind functional substance to glutamine residue, then binding can be achieved, but binding efficiency is not high

Engineering Contradiction:

Improvebinding efficiencyVSAvoidbinding success rate

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent changes the molecular weight parameter of the PEG chain in the bifunctional linker to 1100 or larger, which optimizes the linker's physical and chemical properties for the TG-catalyzed reaction, thereby significantly improving binding efficiency and success rate

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses a composite linker structure combining PEG chain with specific molecular weight, thiol group, and amino group, creating a multifunctional molecule that enhances both the efficiency and reliability of the binding reaction

Inventive Principle:

Principle #40Composite materials

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 method enables highly efficient labeling of polypeptides, enhancing the binding efficiency of functional substances and facilitating the detection of target substances by forming immune complexes with detectable signals.

Implementation Method 1

Transglutaminase (TG) is an enzyme that recognizes a glutamine residue in a polypeptide as a substrate, and catalyzes a reaction between a carboxamide side chain of the glutamine residue and an amino group of a primary amine

Methodology Applied

Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

the amino group in the carboxamide side chain of the glutamine residue in the polypeptide condenses with the primary amine, and a substituent on the primary amine is transferred to the glutamine residue, to produce ammonia

Methodology Applied

Scientific EffectAmide bond formation: Chemical Bonding

Implementation Method 3

followed by attachment of a maleimide group-containing label

Methodology Applied

Scientific EffectThioether bond formation: Chemical Bonding

Data Source

PatentEP4296672B1Labeled polypeptide, modified polypeptide, production method for these polypeptides, reagent containing these polypeptides, and measurement method for target substance

Publication Date: 2024.11.13 SYSMEX CORP

Figure 1A~1B
Figure 2A
Figure 2B

AI summary

Disclosed is a labeled polypeptide that includes a glutamine residue having a side chain represented by formula (I) below: (wherein, (C) represents an α-carbon of the glutamine residue, X represents a straight chain alkylene group, Y represents a polyethylene glycol chain, Z represents a label, L represents a spacer or an atomic bond, and the polyethylene glycol chain has a molecular weight of 1100 or larger).