AQUA Peptides for Methylation Site Detection
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Solution Overview
Problem
Current methods lack effective tools for identifying and modulating arginine and lysine methylation and acetylation sites, which are crucial for understanding and treating diseases such as cancer, due to limited diagnostic and therapeutic targets.
Innovation Solution
The disclosure provides arginine and lysine methylation and acetylation sites in human cell lines, mouse tissues, and human serum, along with specific peptides and antibodies that bind to these sites, enabling detection, quantitation, and modulation of these modifications, including the use of Heavy-Isotope Labeled Peptides (AQUA peptides) and methylation or acetylation site-specific antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods are used for identifying methylation and acetylation sites, then the process is simple, but the detection precision and quantitation capability are insufficient
Solution Approach 1:
The patent employs Heavy-Isotope Labeled Peptides (AQUA peptides) as intermediary standards that co-elute with native peptides during LC separation. These labeled peptides serve as internal references for mass spectrometry quantitation, enabling precise measurement of methylation and acetylation site abundances without requiring complex absolute quantitation methods
Solution Approach 2:
The patent replaces traditional mechanical/chemical quantitation methods with mass spectrometry-based detection. By using tandem mass spectrometry (LC-MS/MS) to detect and quantify peptides containing methylation or acetylation sites, the method achieves high precision without requiring complex chemical labeling or physical separation techniques
2Adaptability or versatility
If specific antibodies and peptides are developed for each methylation and acetylation site, then the detection capability is improved, but the manufacturing complexity and cost increase
Solution Approach 1:
The patent develops a universal platform using Heavy-Isotope Labeled Peptides that can be applied to any methylation or acetylation site. Rather than creating site-specific antibodies for each modification, the AQUA peptide approach provides a multi-functional solution where the same mass spectrometry methodology can detect and quantify multiple different post-translational modifications across various proteins
Solution Approach 2:
The patent creates synthetic Heavy-Isotope Labeled Peptides that are identical copies of native peptides containing methylation or acetylation sites, but with heavy isotopes incorporated. These copied peptides serve as stable, non-degradable standards that can be manufactured reproducibly and used across multiple experiments without the complexity of producing site-specific antibodies
3Quantity of substance
If more methylation and acetylation sites are identified, then the therapeutic targets increase, but the difficulty of detecting and measuring these sites increases
Solution Approach 1:
The patent segments the complex task of detecting post-translational modifications by focusing on specific peptide sequences containing methylation or acetylation sites. By digesting proteins into peptides and detecting only those containing the modifications of interest, the method makes it feasible to identify and quantify numerous sites across the proteome without being overwhelmed by the complexity of analyzing entire proteins
Solution Approach 2:
The patent implements a feedback mechanism where Heavy-Isotope Labeled Peptides are added to samples as internal standards before processing. These standards co-extract and co-elute with native peptides, providing real-time feedback on extraction efficiency, instrument performance, and quantitation accuracy, thereby simplifying the detection of multiple modification sites
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
These tools allow for precise detection and modulation of methylation and acetylation states, providing new diagnostic and therapeutic targets for diseases like cancer, enabling the inhibition of tumor growth, cancer cell proliferation, and angiogenesis.
Implementation Method 1
antibodies that specifically bind at a methylation or acetylation site
Implementation Method 2
Heavy-Isotype Labeled Peptides (AQUA peptides) comprising a methylation or acetylation site
Data Source
AI summary
The disclosure features over 5000 methylation and acetylation sites identified in human cell line, human serum and mouse tissues, peptides (including AQUA peptides) comprising a methylation or acetylation site of the disclosure, antibodies specifically bind to a methylation or acetylation site of the disclosure, and diagnostic and therapeutic uses of the above.