Chemoselective Peptide Tagging Booster for Attomolar MS Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing mass spectrometry methods struggle to accurately map and sequence peptides in protein bioconjugates due to partial digestion, limited ionization, and suppression by other ions, leading to incomplete detection and uncertain labeling confirmation.
Innovation Solution
A chemoselective sensitivity booster comprising sp2 or sp3 nitrogen centers with hydrophobic carbon chains is used to tag peptides, enhancing detection sensitivity to attomolar concentrations and simplifying MS-MS fragmentation patterns.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If mass spectrometry is used for peptide mapping, then structural information can be obtained, but detection sensitivity is insufficient and peptides are not completely detected due to partial digestion, limited ionization, and ion suppression
Solution Approach 1:
The patent introduces an intermediary reagent (sensitivity booster) that mediates between the peptide and the mass spectrometry detection system. This reagent contains a hydrophobic domain that enhances ionization efficiency and a charged domain that improves detectability, thereby resolving the contradiction between obtaining structural information and achieving complete detection of all peptides
Solution Approach 2:
The patent modifies the physical and chemical parameters of peptides by attaching sensitivity booster reagents with specific hydrophobicity and charge characteristics. This parameter change transforms low-detectability peptides into high-detectability analytes, enabling complete peptide mapping while maintaining structural information acquisition
2Measurement precision
If a sensitivity booster with strong hydrophobicity is used, then detection sensitivity improves, but non-specific binding increases
Solution Approach 1:
The sensitivity booster reagent is designed with local quality differentiation: a hydrophobic domain for enhancing ionization and detection sensitivity, and a charged domain for providing solution stability and reducing non-specific binding. This spatial separation of functions resolves the contradiction between improving detection sensitivity and minimizing non-specific binding
Solution Approach 2:
The patent employs a composite molecular structure combining hydrophobic and charged domains within a single sensitivity booster reagent. This composite design allows the molecule to simultaneously provide enhanced detectability through hydrophobic interactions while maintaining solubility and reducing non-specific binding through charged interactions
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 booster improves peptide detection sensitivity and sequence coverage, enabling unambiguous sequencing and identification of labeled sites in peptides, proteins, and bioconjugates, with enhanced signal separation and simplified fragmentation spectra.
Implementation Method 1
comprises sp2 or sp3 nitrogen centers in combination with hydrophobic carbon chains linked with an electrophile or nucleophile for attachment with a peptide, peptide conjugate, or molecules with similar reactivity
Data Source
AI summary
The invention pertains to chemoselective sensitivity booster for tagging a peptide, peptide conjugate, or similar reactive molecule for analysis of a peptide, protein, antibody, protein bioconjugate, antibody bioconjugate, and similar analytes. The sensitivity booster comprises of sp2 or sp3 nitrogen centers in combination with hydrophobic carbon chains linked with an electrophile or nucleophile for attachment with a peptide, peptide conjugate, or molecules with similar reactivity.