Protected Amine Labels for Quantitative Proteomics
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Solution Overview
Problem
Current methods for quantitative proteomics face limitations such as limited dynamic range, incompatibility with certain proteins, and high errors due to gel-to-gel variability in 2DGE, and existing chemical labels often suffer from incomplete incorporation, fragmentation, and reduced ionization efficiency in MS/MS analysis.
Innovation Solution
Development of novel amino acid-based compounds, specifically Protected Amine Labels (PAL), which are isotopically enriched and designed to efficiently label peptides at primary amines, maintaining ionization efficiency and fragmentation patterns, and allowing for complete derivatization and aqueous stability, enabling accurate mass spectrometry analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If 2DGE is used for quantitative proteomics, then protein separation is achieved, but gel-to-gel variability causes high errors
Solution Approach 1:
The patent replaces the mechanical 2DGE separation system with a chemical labeling system based on mass spectrometry. Proteins are labeled with stable isotope tags and quantified by measuring mass ratios in MS spectra, eliminating gel-to-gel variability and achieving more reliable quantitative results.
2Productivity
If existing chemical labels are used, then peptide labeling is achieved, but incomplete incorporation and fragmentation occur
Solution Approach 1:
The patent modifies the chemical parameters of existing labels by incorporating stable isotopes (13C, 15N, 18O) into the labeling reagents. This changes the mass-to-charge ratio of labeled peptides, enabling complete incorporation to be verified and fragmented ions to be distinguished from intact labeled peptides through their characteristic mass shifts.
3Difficulty of detecting and measuring
If chemical labels are used for MS/MS analysis, then peptide identification is achieved, but ionization efficiency is reduced
Solution Approach 1:
The patent applies local quality by designing labels with specific functional groups (carboxylic acid, hydroxyl, or amine groups) that can be positioned at different locations on the peptide molecule. This allows optimization of ionization efficiency at the labeling site while maintaining the overall detectability of the peptide in MS/MS analysis.
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
PAL compounds provide a flexible molecular architecture for stable isotope-based labeling, ensuring high-yield synthesis, compatibility with aqueous solutions, and maintaining peptide hydrophobicity and fragmentation patterns, thus enhancing the accuracy and efficiency of quantitative proteomics analysis.
Implementation Method 1
reacting the one or more molecules with the amino acid based compound
Implementation Method 2
characterising the one or more molecules by mass spectrometry
Data Source
AI summary
The invention is directed towards novel amino acid based compounds, which may be isotopically enriched, and methods of use of such compounds for characterizing one or more molecules of a sample by mass spectrometry, the method comprising: (a) reacting the one or more molecules with the compound; and (b) characterizing the one or more molecules by mass spectrometry.